Gynecology_Novak

Gynecology_Novak. DMPA suppresses ovarian estrogen production. Prospective studies demonstrated bone loss during DMPA therapy, with recovery of bone mass after DMPA use is discontinued (229). Similar bone loss and then recovery occurs with lactation. Adolescents are of special concern because they normally gain bone mass; most of adult bone mass is attained by age 20. Estrogen injections prevent the bone loss and allow adolescent women to gain bone density despite use of DMPA (230). A long-term study in adolescents documented bone density loss and confirmed recovery of lumbosacral bone mineral density to baseline by 60 weeks after discontinuation of DMPA and significant gain above baseline by 180 weeks. Recovery of density at the hip was slower, 240 weeks to significant gain (231). A systematic review of DMPA clinical trials could find no studies where fracture was an outcome, so whether long-term use leads to fractures is still not known (232). The FDA black box warning added to DMPA labeling proposes


Gynecology_Novak

Gynecology_Novak. clinical trials could find no studies where fracture was an outcome, so whether long-term use leads to fractures is still not known (232). The FDA black box warning added to DMPA labeling proposes that DMPA treatment be limited to 2 years at a time, unless the patient has no other good options for contraception. For many women, especially in third world countries, DMPA is often the only option for highly effective contraception because it is inexpensive and easy to administer. The issue should be discussed with women who are considering DMPA, but DMPA should not be routinely discontinued after 2 years unless the patient wants to conceive or wants to change to another contraceptive method for other reasons.


Gynecology_Novak

Gynecology_Novak. The effect of DMPA on plasma lipids is inconsistent; DMPA users appear to have reduced total cholesterol and triglyceride levels, slight reduction in HDL cholesterol, and no change or slight increase in LDL cholesterol, all of which are consistent with a reduction in circulating estrogen levels. In some studies, the decrease in HDL and increase in LDL are statistically significant, although the values remain within normal ranges (233). DMPA is not associated with myocardial infarction. Glucose tolerance tests disclose a small elevation of glucose in DMPA users.


Gynecology_Novak

Gynecology_Novak. There is no change in hemostatic parameters, with the exception that antithrombin III levels are sometimes reduced with chronic therapy (233). Venous thrombosis and thromboembolism have occurred in women on DMPA, but this is very rare (234). As noted earlier, large epidemiologic studies have not found DMPA to be associated with thrombosis (130). Thrombotic episodes occurred in elderly women with advanced cancer who were treated with a variety of agents, including DMPA and tamoxifen (235). Another episode occurred in a woman with a cerebral metastasis from breast cancer (236). Such patients are at high risk for thrombosis regardless of the use of DMPA. Two cases of retinal vein thrombosis were reported. Both women were hypertensive and one of them smoked cigarettes (237). DMPA is not associated with teratogenesis (238). Nor is it associated with affective disorders or mood changes (239).


Gynecology_Novak

Gynecology_Novak. There is widespread support for use of DMPA during lactation when the DMPA is initiated at or after 6 weeks postpartum. There is good evidence that neither infant growth nor lactation is impaired by DMPA or progestin-only oral contraceptives (240). There is continued controversy as to how early DMPA should be given after delivery. Because lactation occurs in response to falling maternal estrogen and progesterone levels after birth, administration of DMPA in the first few days theoretically might interfere with the initiation of lactation. There is concern about the possible neonatal effects of the progestin, but investigators were unable to demonstrate the presence of DMPA or its metabolites in the urine of infants whose mothers received DMPA or any other suppression of reproductive hormones (240). In the United States, DMPA is commonly started at the time of hospital discharge, 48 to 72 hours after delivery. There is urgent need for controlled trials of immediate DMPA compared to


Gynecology_Novak

Gynecology_Novak. (240). In the United States, DMPA is commonly started at the time of hospital discharge, 48 to 72 hours after delivery. There is urgent need for controlled trials of immediate DMPA compared to other contraceptive options to determine whether this practice has an adverse effect on the initiation of lactation. The “U.S. Medical Eligibility Criteria for Contraceptive Use 2010” considers DMPA use prior to 1 month postpartum as category 2: the benefit is thought to exceed the theoretical risk (7).


Gynecology_Novak

Gynecology_Novak. Use of DMPA is not associated with cervical cancer (241). Neither is it associated with ovarian cancer (242). Risk of endometrial cancer is substantially reduced by past use of DMPA (243). A large study found no increase in breast cancer risk among DMPA users (244). DMPA has many of the noncontraceptive benefits of combination oral contraceptives (245). Decreases in anemia, PID, ectopic pregnancy, and endometrial cancer are reported. DMPA is reported to benefit women with sickle cell disease.


Gynecology_Novak

Gynecology_Novak. Subcutaneous DMPA Depo-subQ Provera 104, a lower-dose DMPA preparation for subcutaneous administration, received FDA approval in 2005. The total dose is 30% less than that of the older DMPA intramuscular preparation. Because the dose is administered subcutaneously, blood levels are adequate to completely suppress ovulation for more than 13 weeks in all subjects tested, with a mean time of 30 weeks for return to ovulatory function (246). Contraception efficacy is superb, with no pregnancies in a total of 16,023 woman-cycles in the phase III studies done in the United States (247). Blood levels were lower in very obese women but still sufficient to completely suppress ovulation. The weight gain reported with the 150 mg DMPA remains a problem with the lower dose DMPA. Mean weight gain was 1.59 kg in the first year of use. Loss of bone density was observed with this dosage of DMPA, as with the larger intramuscular dose.


Gynecology_Novak

Gynecology_Novak. Once-a-Month Injectable A once-a-month injectable contraception containing only 25 mg of DMPA in combination with 5 mg of the long-acting estrogen estradiol cypionate was brieﬂy available in the United States, but was withdrawn by the manufacturer because of a packaging problem (248). Originally developed by the World Health Organization, it is described as CycloFem or CycloProvera in the literature and was marketed in the United States as Lunelle (249). Given once a month, this combination produces excellent contraceptive effects. Monthly withdrawal bleeding is similar to a normal menses, leading to high continuation rates despite the need for a monthly injection. Monthly injectable combinations continue to be widely used outside the United States.


Gynecology_Novak

Gynecology_Novak. Subdermal Implants Three progestin-releasing subdermal implants systems are in use worldwide: Jadelle™, Sino-Implant II™, and Implanon™. All three offer long-acting contraception that requires no continuing action by the user and are, hence, forgettable. All are very highly effective and have no serious risk. Each can produce irregular bleeding, which is the principal reason for discontinuation. The mechanism of action is suppression of ovulation in the initial years of use, plus thickening of the cervical mucus that prevents sperm penetration.


Gynecology_Novak

Gynecology_Novak. The original levonorgestrel implant (Norplant™) six-rod system was replaced with a two-rod version (Jadelle™), which is identical in its release rate and clinical activity to Norplant™ and is easier to insert and remove (250). Jadelle™ is widely used around the world. It is approved by the FDA but is not marketed in the United States. It is approved for 5 years. The Sino-Implant II™ is a less expensive two-rod levonorgestrel system manufactured in China and available in several countries. It is effective for 4 years (251). Implanon™ is the only subdermal implant sold in the United States. It is a single rod system containing etonogestrel, the active metabolite of desogestrel. Because of the greater potency of etonogestrel, the single rod releases enough to completely inhibit ovulation for at least 3 years. The single-rod system is most easily inserted and removed. In a United States trial, mean time for insertion was only a half minute and removal required a mean time of 3.5 minutes


Gynecology_Novak

Gynecology_Novak. at least 3 years. The single-rod system is most easily inserted and removed. In a United States trial, mean time for insertion was only a half minute and removal required a mean time of 3.5 minutes (252).


Gynecology_Novak

Gynecology_Novak. A systematic review of 29,972 women and 28,108 woman-months of follow-up with Norplant™, Jadelle™, or Implanon™ found no differences in pregnancies or continuation rate over 4 years. No pregnancies occurred in any of the trials. There were no differences in side effects or adverse events. The most common side effect was unpredictable vaginal bleeding (253).


Gynecology_Novak

Gynecology_Novak. In 923 women followed for 20,648 treatment cycles in 11 studies there were no pregnancies with Implanon™ in place. Six pregnancies occurred within 14 days of removal of the devices. When these are included, as required by FDA, the cumulative Pearl index was 0.38 pregnancies per 100 woman-years at 3 years (254). Irregular bleeding was a problem, but occurred most frequently in the first 90 days of use and decreased over time. In a randomized comparison with the six-rod Norplant™, Implanon™ users had less frequent vaginal bleeding, but more became amenorrheic (255). Other commonly reported side effects are headache, weight gain, acne, breast tenderness, and emotional lability (254). Only 2.3% of subjects discontinued because of weight gain. Most women can use Implanon™. The US MEC lists only a small number of conditions as category 3, and these are based on theoretical concerns without actual evidence of harm (7). Insertion in the immediate postpartum period appears to have no adverse


Gynecology_Novak

Gynecology_Novak. a small number of conditions as category 3, and these are based on theoretical concerns without actual evidence of harm (7). Insertion in the immediate postpartum period appears to have no adverse effects on mother or infant (256).


Gynecology_Novak

Gynecology_Novak. Bone density is not affected by Implanon™, probably because ovarian follicular activity is not totally suppressed and estradiol synthesis continues (257). Enlarged follicular ovarian cysts are common during the first year of use of Jadelle™or Implanon™ and usually resolve spontaneously (258).


Gynecology_Novak

Gynecology_Novak. A comparative study of coagulation and fibrinolytic factors in users of etonogestrel and levonorgestrel implants showed no significant changes from baseline, with the exception of a modest increase in antithrombin III (ATIII)and a small decrease in factor VII activity, changes that might reduce coagulability. Lipid levels and liver function studies were not changed, with the exception of small elevations of bilirubin, with somewhat more observed in levonorgestrel users than etonogestrel users (259). Another study of hemostatic factors found modest decreases in many measurements, within the range of normal, and a modest reduction in the generation of thrombin in users of the etonogestrel implant (260). Taken together these studies provide considerable reassurance that the progestin implants do not increase thrombosis risk. With several million women now using the implants, there are no published studies linking either implant to venous thrombosis or myocardial infarction. Strokes were


Gynecology_Novak

Gynecology_Novak. do not increase thrombosis risk. With several million women now using the implants, there are no published studies linking either implant to venous thrombosis or myocardial infarction. Strokes were reported in users of Norplant™, but case reports do not allow calculation of whether risk is increased from baseline. Attempts to determine stroke risk of users compared to nonusers was inconclusive because so few stroke patients or controls were using the implant (261).


Gynecology_Novak

Gynecology_Novak. Postcoital use of sex steroids to prevent pregnancy began in the 1960s with high-dose estrogen taken daily for 5 days (262). This was replaced with the combination OC containing EE and levonorgestrel for greater convenience (263). More recently levonorgestrel alone became the method of choice after the World Health Organization showed its superiority in a large randomized trial with 1,998 women. The pregnancy rate was 3.2% with the EE/levonorgestrel method and only 1.1% with levonorgestrel alone (RR for pregnancy, 0.32; 95% CI, 0.18–0.70) for women treated within 72 hours of intercourse. Nausea and vomiting occurred much less frequently with levonorgestrel alone (23.1% vs. 50.5%, and 5.6% vs. 18.8%, respectively) (264). The efficacy of both methods declined as the time after intercourse increased. But even after 72 hours, the pregnancy rate with the levonorgestrel treatment was only 2.7% (Fig. 10.9) (265). A single dose of 1.5 mg levonorgestrel is just as effective as two doses of


Gynecology_Novak

Gynecology_Novak. increased. But even after 72 hours, the pregnancy rate with the levonorgestrel treatment was only 2.7% (Fig. 10.9) (265). A single dose of 1.5 mg levonorgestrel is just as effective as two doses of 0.75 mg, has no more side effects, and is more convenient for the patient. Both dosing regimens are FDA approved. Because levonorgestrel is almost as effective at 3 to 5 days after intercourse,


Gynecology_Novak

Gynecology_Novak. Figure 10.9 Emergency contraception: pregnancy rates by treatment group and time since unprotected coitus. LNG, levonorgestrel, 0.75 mg × 2. Yuzpe method is ethinyl estradiol, 0.100 mg plus levonorgestrel 0.50 mg × 2, 12 hours later. (From Randomized controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation. Lancet 1998;352:430 [modified from Table 3], with permission.) the World Health Organization recommends 1.5 mg of levonorgestrel as a single dose, given up to 120 hours after intercourse (266). Research suggests that the main mechanism of action is delay of ovulation. Noe and colleagues established that levonorgestrel works only if it is administered prior to the day of ovulation (267). No pregnancies occurred to 87 women who received levonorgestrel from 1 to 5 days prior to the day of ovulation. Seven pregnancies occurred to 35 women treated on the day of


Gynecology_Novak

Gynecology_Novak. day of ovulation (267). No pregnancies occurred to 87 women who received levonorgestrel from 1 to 5 days prior to the day of ovulation. Seven pregnancies occurred to 35 women treated on the day of ovulation or later. Postcoital levonorgestrel is not an abortifacient because it is effective only when taken before ovulation.


Gynecology_Novak

Gynecology_Novak. Levonorgestrel alone is safer than the estrogen-containing preparations. There were several case reports of thrombotic events after use of the estrogen/levonorgestrel combination emergency contraception (268). No such complications with levonorgestrel alone were published. Antiprogestins The antiprogesterone mifepristone (RU486) is highly effective for postcoital contraception. The usual abortifacient dose is 200 mg, but a dose of only 10 mg is effective for emergency contraception. In one study, 2,065 women were randomized to mifepristone, 10 mg, or levonorgestrel, two doses of 0.75 mg, including women up to 120 hours after intercourse (269). The crude pregnancy rate was 1.3% for mifepristone and 2.0% for levonorgestrel (p = .46). Side effects were the same, and both methods were judged highly acceptable by the patients. Mifepristone is not being developed for this use and is not available at the appropriate dose.


Gynecology_Novak

Gynecology_Novak. Ulipristal, a new progesterone-receptor modulator developed at the U.S. National Institutes of Health was approved by the FDA and the European Union for emergency contraception to 120 hours after intercourse. It is at least as effective as levonorgestrel 1.5 mg up to 72 hours, and may be superior between 72 and 120 hours (270). When Ulipristal is administered prior to the luteinizing hormone (LH) peak, it delays rupture of the preovulatory follicle for 5 days or more, which may be its primary mechanism of action (271). Ulipristal is primarily metabolized by the CYP3A4 enzyme system; hence, patients on drugs such as barbiturates, rifampin, and several of the anticonvulsants may have reduced protection from pregnancy with it. It is a prescription drug, while levonorgestrel 1.5 mg is available over the counter in the United States for women 18 years of age and over. The Copper Intrauterine Device for Emergency Contraception


Gynecology_Novak

Gynecology_Novak. Postcoital insertion of a copper IUD was first reported by Lippes et al. in 1976 (272). In initial trials the device was inserted within 7 days of intercourse and was more effective than steroids for emergency contraception. Studies included women only within 5 days from intercourse. The multicenter trial by Wu and colleagues is an example of the superb efficacy offered by the copper T380A (273). Of 1,893 women who returned for a follow-up visit, there were no pregnancies within 1 month of IUD insertion. Efficacy for emergency contraception is 100% when the device is inserted up to 5 days after intercourse, and almost 100% up to 7 days after intercourse (273). An added benefit was that 94% of the patients were continuing with the IUD at the 12-month follow-up. There were no uterine perforations. Zhou and colleagues reported similar excellent results in a large study with a different copper device, the Multiload Cu-375 IUD (274). In much of the world, copper IUDs are very inexpensive.


Gynecology_Novak

Gynecology_Novak. Zhou and colleagues reported similar excellent results in a large study with a different copper device, the Multiload Cu-375 IUD (274). In much of the world, copper IUDs are very inexpensive. Even in the United States where IUDs are costly, the benefit to the patient of extremely effective emergency contraception, and long-term contraception with one intervention, makes emergency IUDs cost-effective. Whether the levonorgestrel IUD would work for emergency contraception is not known.


Gynecology_Novak

Gynecology_Novak. The same negative feedback of sex steroids that blocks ovulation in women suppresses spermatogenesis in men, but it will produce loss of libido and potentially extinguish sexual performance. The principle was first demonstrated in 1974 using oral estrogen and methyl testosterone (275). Testosterone given alone can suppress sperm production to very low levels while maintaining normal libido and sexual performance. Over many years investigators have studied long-acting testosterone salts for male contraception (276). Ethnicity is an important predictor of efficacy of sperm suppression with testosterone therapy. Asian men virtually always achieve azoospermia or oligospermia when treated with testosterone undecanoate (TU) monthly injections, whereas only 86% of Caucasian men achieved azoospermia or oligospermia or with similar testosterone regimens (277). In a Chinese trial, 1,045 men were treated with monthly TU 500 mg. Only 4.8% failed to suppress to a sperm count less than 1 × 106 per


Gynecology_Novak

Gynecology_Novak. or oligospermia or with similar testosterone regimens (277). In a Chinese trial, 1,045 men were treated with monthly TU 500 mg. Only 4.8% failed to suppress to a sperm count less than 1 × 106 per mL. The cumulative pregnancy rate was only 1.1 per 100 men at 30 months (278). In Caucasian populations testosterone was combined with progestins to further suppress gonadotropin and improve efficacy. In an important trial with Caucasian men, etonogestrel subdermal implants and TU injections were compared to placebo implants and injections. Only 3% failed to suppress to a sperm count of less than 1 × 106 (279). Side effects that were more common in the medicated group than placebo included acne, night sweats, libido changes (usually increased), and weight gain. Theoretical risks include atherogenesis and prostate cancer but long-term trials will be needed to determine if risk is real. Liver cancer is a concern with long-term androgen therapy (280).


Gynecology_Novak

Gynecology_Novak. Surgical sterilization is the most common method of fertility control used by couples, with more than 180 million couples having tubal sterilization or vasectomy (4,281) Laparoscopic and hysteroscopic techniques for women and vasectomy for men are safe and readily available throughout the United States. The mean age at sterilization is 30 years. Age younger than 30 years when sterilized, conﬂict within the marriage, and divorce and remarriage are predictors of sterilization regret, which may lead to a request for reversal of sterilization (281). Female Sterilization Hysterectomy is no longer considered for sterilization because morbidity and mortality are too high in comparison with tubal sterilization. Vaginal tubal sterilization, which was associated with occasional pelvic abscess, is rarely performed in the United States. Five procedures are used in the United States. 1. Tubal sterilization at the time of laparotomy for a cesarean delivery or other abdominal operation 2. 3.


Gynecology_Novak

Gynecology_Novak. 1. Tubal sterilization at the time of laparotomy for a cesarean delivery or other abdominal operation 2. 3. 4. 5. Figure 10.10 Pomeroy technique for tubal sterilization. Postpartum tubal sterilization at the time of cesarean delivery adds no risk other than a slight prolongation of operating time; cesarean birth poses more risk than vaginal birth, and planned sterilization should not inﬂuence the decision to perform a cesarean delivery. Minilaparotomy can be performed in the immediate postpartum state. The uterus is enlarged, and the fallopian tubes lie in the midabdomen, easily accessible through a small, 3-to 4-cm subumbilical incision.


Gynecology_Novak

Gynecology_Novak. Interval minilaparotomy, first described by Uchida, was rediscovered and popularized in the early 1970s in response to an increased demand for sterilization procedures and a simpler alternative to laparoscopy (282). Still widely practiced in lower resource settings, it is uncommon in the United States because of widespread availability of the endoscopic techniques.


Gynecology_Novak

Gynecology_Novak. Surgical Technique The procedure usually elected for tubal sterilization by laparotomy is the Pomeroy or modified Pomeroy technique (Fig. 10.10). In the classic Pomeroy procedure, a loop of tube is excised after ligating the base of the loop with a single absorbable suture. A modification of the procedure is excision of the midportion of the tube after ligation of the segment with two separate absorbable sutures. This modified procedure has several names: partial salpingectomy, Parkland Hospital technique, separate sutures technique, and modified Pomeroy. In the Madlener technique, now abandoned because of too many failures, a loop of tube is crushed by cross-clamping its base, ligated with permanent suture, and then excised. Pomeroy and partial salpingectomy procedures have failure rates of 1 to 4 per 1,000 cases (281). In contrast, pregnancy is almost unheard of after tubal sterilization by the Irving or Uchida methods. In the Irving method, the midportion of the tube is excised,


Gynecology_Novak

Gynecology_Novak. of 1 to 4 per 1,000 cases (281). In contrast, pregnancy is almost unheard of after tubal sterilization by the Irving or Uchida methods. In the Irving method, the midportion of the tube is excised, and the proximal stump of each tube is turned back and led into a small stab wound in the wall of the uterus and sutured in place, creating a blind loop. With the Uchida method, a saline-epinephrine solution (1:1,000) is injected beneath the mucosa of the midportion of the tube, separating the mucosa from the underlying tube. The mucosa is incised along the antimesenteric border of the tube, and a tubal segment is excised under traction so that the ligated proximal stump will retract beneath the mucosa when released. The mucosa is then closed with sutures, burying the proximal stump and separating it from the distal stump. In Uchida’s personal series of more than 20,000 cases, there were no pregnancies (282).


Gynecology_Novak

Gynecology_Novak. Laparoscopy Laparoscopy is the most common method of interval sterilization in the United States. In the standard laparoscopy technique, the abdomen is inﬂated with a gas (carbon dioxide) through a special needle inserted at the lower margin of the umbilicus (281). A hollow sheath containing a pointed trocar is then pushed through the abdominal wall at the same location, the trocar is removed, and the laparoscope is inserted into the abdominal cavity through the sheath to visualize the pelvic organs. A second, smaller trocar is inserted in the suprapubic region to allow the insertion of special grasping forceps. Alternatively, an operating laparoscope that has a channel for the instruments can be used; thus, the procedure can be performed through a single small incision. Laparoscopic sterilization is usually performed in the hospital under general anesthesia but can be performed under local anesthesia with conscious sedation. Overnight hospitalization for laparoscopy is rarely needed.


Gynecology_Novak

Gynecology_Novak. Open Laparoscopy Standard laparoscopy carries with it a small but definite risk for injury to major blood vessels with insertion of the sharp trocar. With the alternative technique of open laparoscopy, neither needle nor sharp trocar is used; instead, the peritoneal cavity is opened directly through an incision at the lower edge of the umbilicus. A special funnel-shaped sleeve, the Hassan cannula, is inserted, and the laparoscope is introduced through it.


Gynecology_Novak

Gynecology_Novak. Techniques for Tubal Closure at Laparoscopy Sterilization is accomplished by any of four techniques: bipolar electrical coagulation, application of a small Silastic rubber band (Falope ring), the plastic and metal Hulka clip, or the Filshie clip. The Filshie clip, first introduced into the United States in 1996 is used extensively in the United Kingdom and Canada (283). It is a hinged device made of titanium with a liner of silicone rubber tubing. Because of its lower pregnancy rate, the Filshie clip has largely supplanted the Hulka clip (284).


Gynecology_Novak

Gynecology_Novak. In the bipolar electrocoagulation technique, the midisthmic portion of the tube and adjacent mesosalpinx are grasped with special bipolar forceps, and radiofrequency electric current is applied to three adjacent areas, coagulating 3 cm of tube (Fig. 10.11). The tube alone is then recoagulated in the same places. The radiofrequency generator must deliver at least 25 watts into a 100-ohm resistance at the probe tips to ensure coagulation of the complete thickness of the fallopian tube and not just the outer layer; otherwise, the sterilization will fail (285).


Gynecology_Novak

Gynecology_Novak. To apply the Falope ring, the midisthmic portion of the tube is grasped, with tongs advanced through a cylindrical probe that has the ring stretched around it (Fig. 10.12A). A loop of tube is pulled back into the probe, and the outer cylinder is advanced (Fig. 10.12B), releasing the Silastic ring around the base of the loop of tube, producing ischemic necrosis (Fig. 10.12C). If the tube cannot be pulled easily into the applicator, the operator should stop and change to electrical coagulation rather than persist and risk lacerating the tube with the Falope ring applicator. The banded tube must be inspected at close range through the laparoscope to demonstrate that the full thickness of the tube was pulled through the Falope ring. Figure 10.11 Technique for bipolar electrocoagulation tubal sterilization. Figure 10.12 Placement of the Falope ring for tubal sterilization.


Gynecology_Novak

Gynecology_Novak. Figure 10.11 Technique for bipolar electrocoagulation tubal sterilization. Figure 10.12 Placement of the Falope ring for tubal sterilization. The Hulka clip is placed across the midisthmus, ensuring that the applicator is at right angles to the tube and that the tube is completely contained within the clip before the clip is closed. The Filshie clip is placed at right angles across the midisthmus, taking care that the anvil of the posterior jaw can be visualized through the mesosalpinx beyond the tube to ensure that the complete thickness of the tube is completely within the jaws of the clip before it is closed (Fig. 10.13).


Gynecology_Novak

Gynecology_Novak. The electric plus band or clip techniques each have advantages and disadvantages. Bipolar coagulation can be used with any fallopian tube. The Falope ring and Hulka and Filshie clips cannot be applied if the tube is thickened from previous salpingitis. There is more pain during the first several hours after Falope ring application. This can be prevented by bathing the tubes with a few milliliters of 2% lidocaine just before ring placement. Failures of the Falope ring or the clips generally result from misapplication, and pregnancy, if it occurs, is usually Risks of Tubal Sterilization


Gynecology_Novak

Gynecology_Novak. Risks of Tubal Sterilization Figure 10.13 Filshie clip for tubal sterilization. (Courtesy of CooperSurgical, Inc., Trumbull, CT.) intrauterine. After bipolar sterilization, pregnancy may result from tuboperitoneal fistula and is ectopic in more than 50% of cases. If inadequate electrical energy is used, a thin band of fallopian tube remains that contains the intact lumen and allows intrauterine pregnancy to occur. Thermocoagulation, the use of heat probes rather than electrical current, is employed extensively in Germany for laparoscopic tubal sterilization but is little used in the United States.


Gynecology_Novak

Gynecology_Novak. Tubal sterilization is remarkably safe. The Collaborative Review of Sterilization (CREST) study, a 1983 review of 9,475 interval sterilizations from multiple centers in the United States, reported a total complication rate of 1.7 per 100 procedures (281). Complications were increased by use of general anesthesia, previous pelvic or abdominal surgery, history of PID, obesity, and diabetes mellitus. The most common significant complication was unintended laparotomy for sterilization after intra-abdominal adhesions were found. In another series, 2,827 laparoscopic sterilizations were performed with the Silastic band using local anesthesia and intravenous sedation (286). Only four cases could not be completed (a technical failure rate of 0.14%), and laparotomy was never needed. Rarely, salpingitis can occur as a complication of the surgery. This occurs more often with electric coagulation than nonelectric techniques. Risk of death with female sterilization was 1 to 2 per 100,000


Gynecology_Novak

Gynecology_Novak. salpingitis can occur as a complication of the surgery. This occurs more often with electric coagulation than nonelectric techniques. Risk of death with female sterilization was 1 to 2 per 100,000 sterilizations in the last national study that was based on data from 1979 to 1980 (281). Almost half of the deaths were from complications of general anesthesia, usually related to the use of mask ventilation. When general anesthesia is used for laparoscopy, endotracheal intubation is mandatory because the pneumoperitoneum increases the risk of aspiration. International data from the Association for Voluntary Surgical Contraception show a similar record of safety from third world programs: 4.7 deaths per 100,000 female sterilizations and 0.5 deaths per 100,000 vasectomies (287).


Gynecology_Novak

Gynecology_Novak. Sterilization Failure Many “failures” occur during the first month after surgery and are the result of a pregnancy already begun when the sterilization was performed. Contraception should be continued until the day of surgery, and a sensitive pregnancy test should be routinely performed on the day of surgery. Because implantation does not occur until 6 days after conception, a woman could conceive just before the procedure and there would be no way to detect it. Scheduling sterilization early in the menstrual cycle obviates the problem but adds to the logistic difficulty. Another cause of failure is the presence of anatomic abnormalities, usually adhesions surrounding and obscuring one or both tubes. An experienced laparoscopic surgeon with appropriate instruments usually can lyse the adhesions, restore normal anatomic relations, and positively identify the tube. In some circumstances successful sterilization will not be possible by laparoscopy, and the surgeon must know before


Gynecology_Novak

Gynecology_Novak. adhesions, restore normal anatomic relations, and positively identify the tube. In some circumstances successful sterilization will not be possible by laparoscopy, and the surgeon must know before surgery whether the patient is prepared to undergo laparotomy, if necessary,


Gynecology_Novak

Gynecology_Novak. Table 10.8 Ten-Year Life-Table Cumulative Probability of Pregnancy per 1,000 Procedures with Different Methods of Tubal Sterilization, United States, 1978–1986 From Peterson HB, Xia Z, Hughes JM, et al. The risk of pregnancy after tubal sterilization: findings from the U.S. Collaborative Review of Sterilization. Am J Obstet Gynecol 1996;174:1164 [Table II], with permission.


Gynecology_Novak

Gynecology_Novak. to accomplish sterilization. The CREST study reported on a cohort of 10,685 women sterilized from 1978 to 1986 at any of 16 participating centers in the United States who were followed from 8 to 14 years (281). The true failure rates for 10 years obtained by the life-table method are given in Table 10.8. Pregnancies resulting from sterilization during the luteal phase of the cycle in which the surgery was performed were excluded. Of all remaining pregnancies, 33% were ectopic. The most effective methods at 10 years were unipolar coagulation at laparoscopy and postpartum partial salpingectomy, generally a modified Pomeroy procedure. Bipolar tubal coagulation and the Hulka-Clemens clip were least effective. The Filshie clip was not evaluated because it was not in use in the United States at the time. Younger women had higher risk for failure, as would be expected because of their greater fecundity.


Gynecology_Novak

Gynecology_Novak. Over the years since the CREST study began, sterilization by unipolar electrosurgery was abandoned because of the risk of bowel burns and was replaced with bipolar electro-surgery or the nonelectric methods (tubal ring, Hulka-Clemens clip, and the Filshie clip). An important later analysis of the CREST data found that bipolar sterilization can have a very low long-term failure rate if an adequate portion of the tube is coagulated. CREST study participants who were sterilized with bipolar electrosurgery from 1985 to 1987 had lower failure rates than those sterilized earlier (1978–1985). The important difference was in the application technique of the electric energy to the tubes. Women whose bipolar procedure involved coagulation at three sites or more had low 5-year failure rates (3.2 per 1,000 procedures), whereas women who had fewer than three sites of tubal coagulation had a 5-year failure rate of 12.9 per 1,000 (p = .01) (288).


Gynecology_Novak

Gynecology_Novak. Family Health International reported large randomized multicenter trials of the different means of tubal sterilization. The Filshie and Hulka clips were compared in two trials. A total of 2,126 women were studied, of which 878 had either clip placed by minilaparotomy and 1,248 had either clip placed by laparoscopy. The women were evaluated at up to 24 months (289). Pregnancy rates were 1.1 per 1,000 women with the Filshie clip and 6.9 per 1,000 with the Hulka clip at 12 months, a difference in rates that approached statistical significance (p = .06). This same group compared the Filshie clip with the Silastic tubal ring in a similar study with a total of 2,746 women, of which 915 had the devices placed at minilaparotomy and 1,831 at laparoscopy (290). Pregnancy rates at 12 months were the same for the Filshie clip and the tubal ring: 1.7 per 1,000 women. The ring was judged more difficult to apply. The Filshie clip was expelled spontaneously from the vagina by three women during the


Gynecology_Novak

Gynecology_Novak. same for the Filshie clip and the tubal ring: 1.7 per 1,000 women. The ring was judged more difficult to apply. The Filshie clip was expelled spontaneously from the vagina by three women during the 12 months of follow-up.


Gynecology_Novak

Gynecology_Novak. Hysteroscopy In 2002, the FDA approved Essure™, a hysteroscopic method of permanent birth control, and a second hysteroscopy method, Adiana™, was approved in 2009. Both methods can be provided in an office setting, with only local anesthesia or conscious sedation and both offer the prospect of greater safety, lower cost, and greater long-term effectiveness than the best laparoscopy methods. Essure™ is a microinsert consisting of a soft stainless steel inner coil and a dynamic nickel titanium alloy outer coil (Fig. 10.14). Soft fibers of polyethylene terephthalate run along and through the inner coil. To insert the device, a hysteroscope is introduced into the uterine cavity, which is distended with saline. The tubal ostia are visualized. The Essure™ device is inserted through the operating channel of the hysteroscope on the end of a slender delivery wire, guided into the tubal opening and advanced into the tube under direct vision (Fig. 10.15). Once in place, an outer sheath is


Gynecology_Novak

Gynecology_Novak. channel of the hysteroscope on the end of a slender delivery wire, guided into the tubal opening and advanced into the tube under direct vision (Fig. 10.15). Once in place, an outer sheath is retracted, releasing the outer coils, which expand to anchor the device in the interstitial portion of the tube. The delivery wire is detached and removed and the procedure repeated for the other tube. When properly placed, three to eight of the end coils of the microinsert are visible inside the uterine cavity. The rest are inside the fallopian tube (291,292).


Gynecology_Novak

Gynecology_Novak. Figure 10.14 Essure device for hysteroscopic sterilization. (Courtesy of Conceptus, Inc.) The Adiana™ system consists of a catheter electrode that is guided into the interstitial portion of the fallopian tube via the operating channel of a 5-mm hysteroscope (Fig. 10.16). An array of bipolar electrodes on the catheter are used to apply radio frequency electric current for 60 seconds to achieve a temperature of 64◦C, creating a superficial injury to the inner surface. A 3.5-mm ﬂexible cylindrical silicone matrix is deployed from the catheter into the tube at the site of the thermal lesion. The same process is repeated in the other tube. A nonionic medium such as 1.5% glycine is used to distend the uterus (293).


Gynecology_Novak

Gynecology_Novak. Essure™ and Adiana™ devices can be installed under local anesthesia in an outpatient setting. No incision is needed. A nonsteroidal anti-inﬂammatory drug is given 1 to 2 hours before the procedure to decrease tubal spasm. Over time fibrous tissue grows into both devices, occluding the tubes permanently. Because of this mechanism of action, these methods depend on scar formation, and women who are immunocompromised from HIV infection, medication, or chemotherapy should be advised that their success may be lower (293,294). The FDA requires a 3-month follow-up x-ray hysterosalpingography examination to document tubal occlusion for both methods. The hysterosalpingogram (HSG) for Essure™ should document bilateral placement of the devices at the uterotubal junction and a lack of peritoneal spillage of dye. Off-label and outside of the United States, plain x-ray, ultrasound, computerized x-ray tomography, and magnetic resonance imaging were used to confirm the presence and position of the


Gynecology_Novak

Gynecology_Novak. of dye. Off-label and outside of the United States, plain x-ray, ultrasound, computerized x-ray tomography, and magnetic resonance imaging were used to confirm the presence and position of the Essure™ devices (295,296). The Adiana™ matrix is not radio opaque, so successful occlusion is documented only by lack of dye spillage. The patient with transcervical sterilization should continue to use a reliable method of contraception until successful occlusion is documented.


Gynecology_Novak

Gynecology_Novak. Figure 10.15 Essure device with guide wire and handle. (Courtesy of Conceptus, Inc.) Figure 10.16 Adiana catheter as placed for tubal sterilization. (Courtesy of Hologic, Inc.)


Gynecology_Novak

Gynecology_Novak. Risks of Hysteroscopy Adverse events or side effects were reported on the day of procedure in 3% of the initial Essure™ patients. These consisted of vasovagal responses, cramping, nausea, and vaginal spotting (297). Possible but uncommon risks of the hysteroscopic tubal sterilization methods include perforation by the device at insertion and expulsion of the device. In the initial clinical trials tubal perforation was reported in 1% of Essure™ placements. None were reported with Adiana™. There is theoretical risk of mutagenic or carcinogenic effect to the fetus from nickel alloy in Essure™ should pregnancy occur, although no such injury was reported (297). Other potential combinations with transcervical sterilization are related to the hysteroscopy procedure, not the tubal occlusion process. These include hypervolemia, injury to surrounding organs, bleeding, and infection and occur in less than 1% of cases. Excessive ﬂuid absorbance leading to hypervolemia is more of a concern with


Gynecology_Novak

Gynecology_Novak. These include hypervolemia, injury to surrounding organs, bleeding, and infection and occur in less than 1% of cases. Excessive ﬂuid absorbance leading to hypervolemia is more of a concern with Adiana™ and the nonionic solution that must be used to distend the uterine cavity because of the electrical energy applied. With Essure™ the distending medium is normal saline (293,294). An extensive 2009 review of the first 6 years of Essure™ use reported in publications, industry sources and the Manufacturer and User Facility Device Experience (MAUDE) database maintained by the FDA, found 20 reports of pelvic pain, which in some cases responded to hysteroscopy or laparoscopic removal of the device. An additional 20 women had second-look hysteroscopy because of persistent abnormal vaginal bleeding. During this time period more than 172,000 Essure™ devices were shipped, so such problems are quite rare (298).


Gynecology_Novak

Gynecology_Novak. Sterilization Failure with Hysteroscopic Methods The Essure™ microinsert was successfully placed in 86% of patients after the first procedure, which increased to 90% after a second procedure using the initial insertion catheter. (298). Reasons for failure of insertion were tubal obstruction, stenosis, or difficulty in accessing the tubal ostia. Correct placement was confirmed at 3 months in 96%, and complete bilateral occlusion occurred in 92%. Of those patients with complete occlusion, there were no pregnancies in 5,305 woman-months of use. A subsequent study of an improved catheter design in 2004 reported a 98% successful placement rate (299). The Adiana™ trials reported a 94% successful placement rate with the first procedure, which increased to 95% after a second procedure (301).


Gynecology_Novak

Gynecology_Novak. As of October 2008, 258 Essure™-related pregnancies were reported to the manufacturer. Most can be attributed to patient or clinician noncompliance with the manufacturer’s instructions, failure to use contraception during the 3-month wait for a HSG, failure to return for the HSG, physician error in interpreting the HSG, and some luteal phase pregnancies. No known pregnancies occurred in the clinical trials when the subjects met the criteria to rely on Essure™ (297). In patients with documented occlusion in the Adiana™ trials, a 1.1% failure rate was reported in the first year of use and a 1.8% failure rate at 2 years (297). Longer-term data are not yet available for Adiana™, but it appears that Essure™ will have a lower long-term pregnancy rate than Adiana™.


Gynecology_Novak

Gynecology_Novak. Reversal of Sterilization Reversal of sterilization is more successful after mechanical occlusion than after electrocoagulation, because the latter method destroys much more of the tube. With modern microsurgical techniques and an isthmus-to-isthmus anastomosis, the first-year pregnancy rate is about 44% (301). A retrospective review comparing microsurgical reanastomosis to in vitro fertilization (IVF) found similar total pregnancy rates, but a higher live birthrate with IVF because 10% of the pregnancies after microsurgery were ectopic (301). Hysteroscopic sterilization by the Essure™ and Adiana™ procedures should be considered irreversible. Reversal was not reported and would have to involve cornual resection and reimplantation of the fallopian tubes, a procedure with a very low success rate. IVF appears to be the only alternative for these women. Late Sequelae of Tubal Sterilization


Gynecology_Novak

Gynecology_Novak. Increased menstrual irregularity and pain are attributed to previous tubal sterilization. Study of the problem is complicated by the fact that many women develop these symptoms as they age, even though they did not have tubal surgery and are treated with OCs that reduce pain and create an artificially normal menstrual cycle. Women who discontinue OC use after tubal sterilization will experience more dysmenorrhea and menstrual irregularity, which is unrelated to the sterilization. The best answer available comes from the CREST study (302). A total of 9,514 women who underwent tubal sterilization were compared with 573 women whose partners had undergone vasectomy. Both groups were followed up to 5 years with annual standardized telephone interviews. Women who underwent tubal sterilization were no more likely to report persistent changes in intermenstrual bleeding or length of the menstrual cycle than women whose partners had vasectomy. The sterilized women reported decreases in days of


Gynecology_Novak

Gynecology_Novak. no more likely to report persistent changes in intermenstrual bleeding or length of the menstrual cycle than women whose partners had vasectomy. The sterilized women reported decreases in days of bleeding, amount of bleeding, and menstrual pain but were slightly more likely to report cycle irregularity (OR, 1.6; 95% CI, 1.1–2.3). In summary, the CREST study provided good evidence that there is no posttubal ligation syndrome.


Gynecology_Novak

Gynecology_Novak. Noncontraceptive Benefits of Tubal Sterilization In addition to providing excellent contraception, tubal ligation is associated with reduced risk for ovarian cancer that persists for as long as 20 years after surgery (303).


Gynecology_Novak

Gynecology_Novak. In addition to providing excellent contraception, tubal ligation is associated with reduced risk for ovarian cancer that persists for as long as 20 years after surgery (303). Vasectomy About 500,000 vasectomies are performed each year in the United States (281). Vasectomy is a highly effective method. The literature on efficacy is often difficult to interpret because most studies report failure as failure to achieve azoospermia, rather than long-term pregnancy rates among the relevant women. Vasectomy is not effective until all sperm are cleared by the reproductive tract. It is estimated that up to half of pregnancies after vasectomy occur during this time (304). In addition, not all pregnancies after vasectomy can be attributed to the men who had the operation. The best long-term information comes from the CREST study. The cumulative probability of failure was 7.4 per 1,000 procedures at 1 year and 11.3 at year 5, and comparable to the failure rate of tubal sterilization (281).


Gynecology_Novak

Gynecology_Novak. Vasectomy is usually performed under local anesthesia. The basic technique is to palpate the vas through the scrotum, grasp it with fingers or atraumatic forceps, make a small incision over the vas, and pull a loop of the vas into the incision. A small segment is removed, and then a needle electrode is used to coagulate the lumen of both ends. Improved techniques include the no-scalpel vasectomy, in which the pointed end of the forceps is used to puncture the skin over the vas. This small variation reduces the chance of bleeding and avoids the need to suture the incision. Another variation is the open-ended vasectomy, in which only the abdominal end of the severed vas is coagulated while the testicular end is left open. This is believed to prevent congestive epididymitis (305). Fascial interposition can be used with any of the above techniques and is widely believed to reduce recanalization. This technique involves securing the thin layer of tissue that surrounds the vas over one of


Gynecology_Novak

Gynecology_Novak. can be used with any of the above techniques and is widely believed to reduce recanalization. This technique involves securing the thin layer of tissue that surrounds the vas over one of the cut ends (306).


Gynecology_Novak

Gynecology_Novak. Reversibility Vasectomy must be regarded as a permanent means of sterilization; however, with micro-surgical techniques, vasovasostomy will result in pregnancy about half of the time. The longer the interval since vasectomy, the poorer is the chance of reversal.


Gynecology_Novak

Gynecology_Novak. Safety Operative complications include scrotal hematomas, wound infection, and epididymitis, but serious sequelae are rare. There were no reports of deaths from vasectomy in the United States in many years, and the death rate in a large third world series was only 0.5 per 100,000. Studies of vasectomized monkeys showed accelerated atherosclerosis, but several large-scale human studies found no connection between vasectomy and vascular disease (307). There is no evidence of cardiovascular risk even 20 years after the operation (308). Concerns about long-term safety recurred with the report of a possible association between prostate cancer and vasectomy (309). Recent large studies present the very clear conclusion that vasectomy is not associated with prostate cancer (310–312).


Gynecology_Novak

Gynecology_Novak. It is extremely likely that normal couples will experience at least one unwanted pregnancy at some time during their reproductive years. In third world countries, desired family size is larger, but access to effective contraception is limited. As a result, abortion is common. While there was a decline in the overall number of abortions worldwide from 46 million in 1995 to 42 million in 2003, this decline was greater in developed than in developing countries. About half of induced abortions are illegal and considered “unsafe” by the World Health Organization definition: procedures carried out either by an unskilled person or in unsafe conditions or both (313,314).


Gynecology_Novak

Gynecology_Novak. As shown in Table 10.9 total abortion rates are quite similar over much of the world. What differs is the rate of safe abortions compared with unsafe abortions. In the developed countries, unsafe abortions are rare. In the developing countries they are very common. The highest rates of unsafe abortion are in Latin America and Africa, where abortion is generally illegal. North America, where abortion is legal and contraceptive use is high, has a lower abortion rate, 21 per 1000 women of reproductive age. Abortion rates are even lower in Western Europe, 12 per 1000 (314). Where abortion is legal, it is generally safe; where it is illegal, complications are common. Seventy thousand women die every year from complications of unsafe abortion. Societies cannot prevent abortion, but they can determine whether it will be illegal and dangerous or legal and safe. Death from illegal abortion was once common in the United States. In the 1940s, more than 1,000 women died each year of complications


Gynecology_Novak

Gynecology_Novak. whether it will be illegal and dangerous or legal and safe. Death from illegal abortion was once common in the United States. In the 1940s, more than 1,000 women died each year of complications from abortion


Gynecology_Novak

Gynecology_Novak. Table 10.9 Estimated Numbers and Rates of Safe and Unsafe Abortion Worldwide, by Region and Subregion, 2003 Number of abortions (millions) Abortion ratea aAbortions per 1,000 women aged 15–44. From Sedgh G, Henshaw S, Singh S, et al. Induced abortion: estimated rates and trends worldwide. Lancet 2007;370:1338–1345 [Table 2. P1342], with permission.


Gynecology_Novak

Gynecology_Novak. (315). In 1972, 24 women died of complications of legal abortion and 39 died from known illegal abortions. In 2005, the most recent year for which complete data are available, there were seven deaths from legally induced abortion and no deaths from illegal abortion (abortion induced by a nonprofessional) in the entire United States (316). The American Medical Association’s Council on Scientific Affairs reviewed the impact of legal abortion and attributes the decline in deaths during this century to the introduction of antibiotics to treat sepsis; the widespread use of effective contraception beginning in the 1960s, which reduced the number of unwanted pregnancies; and the shift from illegal to legal abortion (317). The United States has a serious problem with teenage pregnancy. Without legal abortion, there would be almost twice as many teenage births each year.


Gynecology_Novak

Gynecology_Novak. The number of abortions reported each year in the United States—1.2 million in 2006—has been declining since the peak level of 1.61 million in 1990. In 2006, the national abortion ratio was 22.4 abortions for every 1,000 live births, and the national abortion rate was 19.4 per 1,000 women aged 15 to 44 years (318). While abortion rates for all racial and ethnic groups have declined, they are significantly higher for black and Hispanic women. Non-Hispanic white women have 22% of all abortions, black women have 37%, and Hispanic women 22%. Most women who obtain abortions are unmarried, 83.5% in 2006 (316). Use of abortion varies markedly with age. In 2006, 16.9% of women obtaining abortions were between 15 and 19 years of age, and 49.6% were 24 years of age or younger. In 2006, the abortion ratio for women younger than 15 years of age was 759 per 1,000 live births, almost as many abortions as births (Fig. 10.1). The lowest abortion ratio, 141 per 1,000 live births, is for women aged 30


Gynecology_Novak

Gynecology_Novak. ratio for women younger than 15 years of age was 759 per 1,000 live births, almost as many abortions as births (Fig. 10.1). The lowest abortion ratio, 141 per 1,000 live births, is for women aged 30 to 34 years.


Gynecology_Novak

Gynecology_Novak. Regardless of personal feelings about the ethics of interrupting pregnancy, health professionals have a duty to know the medical facts about abortion and to share them with their patients (319). Providers are not required to perform abortions against their ethical principles, but they have a duty to help patients assess pregnancy risks and to make appropriate referrals.


Gynecology_Novak

Gynecology_Novak. Safety The overall annual risk of death with legal abortion decreased markedly, from 4.1 per 100,000 in 1972 to 1.8 in 1976, and remained less than 1 per 100,000 since 1987. Risk of death with vacuum curettage was 0.1 per 100,000 at or before 8 weeks in 1993 to 1997 and 0.2 per 100,000 at 9 to 10 weeks (320). Risk increases exponentially with gestational age, reaching 2.7 per 100,000 for dilatation evacuation abortion at 16 to 20 weeks and 7.2 per 100,000 at 21 weeks or more. The maternal mortality rate in the United States is 12.7 per 100,000 (321); hence, abortion by dilation and evacuation (D&E) through 20 weeks’ gestation is safer than continuing pregnancy. It was estimated that 87% of the legal abortion deaths occurring after 8 weeks would have been prevented had the woman been able get abortion services by 8 weeks (322).


Gynecology_Novak

Gynecology_Novak. For individual women with high-risk conditions (e.g., cyanotic heart disease), even late abortion is a safer alternative to birth. Because of the availability of low-cost, out-of-hospital, first-trimester abortion, 88% of legal abortions are performed during the first trimester (before 13 weeks of amenorrhea), when abortion is the safest.


Gynecology_Novak

Gynecology_Novak. Vacuum Curettage Most first-trimester abortions are performed by vacuum curettage. Most are performed with local anesthesia with or without conscious sedation, and usually on an outpatient basis in a freestanding specialty clinic or doctor’s office (323). Cervical dilatation is accomplished with metal dilators, or by laminaria tents or misoprostol, 400 μg, given vaginally or by the buccal route 3 to 4 hours before the procedure (324). A plastic vacuum cannula of 5-to 12-mm diameter is used with a manual vacuum source or an electric vacuum pump. Manual vacuum provided by a modified 50-mL syringe is as effective as the electric pump through 10 menstrual weeks (325). Doxycycline is given to prevent infection and has proven effective (326). Complications of a large number of vacuum curettage procedures before 14 weeks of gestation from Planned Parenthood of New York City are presented in Table 10.10. Mild infection not requiring hospitalization and retained tissue or clot requiring


Gynecology_Novak

Gynecology_Novak. procedures before 14 weeks of gestation from Planned Parenthood of New York City are presented in Table 10.10. Mild infection not requiring hospitalization and retained tissue or clot requiring resuctioning in the clinic were the most common complications. Somewhat less than 1% experienced any complications, and less than 1 per 1,000


Gynecology_Novak

Gynecology_Novak. Table 10.10 Complications of 170,000 First-Trimester Abortions aCausing amenorrhea. bAfter local anesthesia. cRequiring hospitalization.dTwo or more days of fever 40◦C or higher. eIntrauterine and tubal pregnancy. Adapted from Hakim-Elahi E, Tovel HM, Burnhill HM, et al. Complications of first trimester abortion: a report of 170,000 cases. Obstet Gynecol 1990:76:129–135. were hospitalized (327). More extensive descriptions of the management of complications are published elsewhere (328,329).


Gynecology_Novak

Gynecology_Novak. Mifepristone (RU486), an analogue of the progestin norethindrone, has strong affinity for the progesterone receptor but acts as an antagonist, blocking the effect of natural progesterone. Given alone, the drug was moderately effective in causing abortion of early pregnancy; the combination of mifepristone with a low dose of prostaglandin proved very effective, producing complete abortion in 96% to 99% of cases (330). The FDA approved a protocol of mifepristone, 600 mg orally, followed 2 days later by misoprostol, 400 mg, taken orally in women no more than 49 days from start of the last menstrual period. In the years before FDA approval, investigators established the superiority of the evidence-based protocols that are used. These protocols used 200 mg of mifepristone rather than 600 mg, because the lower dose is just as effective. Misoprostol, 800 μg is given by vaginal or buccal routes, which provides higher efficacy than the 400 μg oral dose (331–334). The misoprostol can be taken


Gynecology_Novak

Gynecology_Novak. because the lower dose is just as effective. Misoprostol, 800 μg is given by vaginal or buccal routes, which provides higher efficacy than the 400 μg oral dose (331–334). The misoprostol can be taken at 24, 48, or 72 hours after mifepristone with equal efficacy (333). Women may safely self-administer the misoprostol at home (334). It can be taken by buccal or vaginal routes with similar blood levels and similar areas under the plasma concentration curve (AUC) (335,336). After case reports of death from Clostridium sordelli, a large cohort study was published by Planned Parenthood describing use of prophylactic doxycycline 100 mg twice a day for one week, and buccal rather than vaginal administration of misoprostol (337).


Gynecology_Novak

Gynecology_Novak. Contraindications to medical abortion with mifepristone/misoprostol include ectopic pregnancy; an IUD in place (remove IUD first); chronic adrenal failure; concurrent longterm corticosteroid therapy; history of allergy to mifepristone, misoprostol, or other prostaglandin; and the inherited porphyrias (338). The mifepristone–misoprostol combination was studied for gestations at 9 to 13 weeks; although it is almost as effective as earlier in pregnancy, a larger proportion of patients will experience heavy bleeding and require vacuum curettage (339).


Gynecology_Novak

Gynecology_Novak. Alternatives to medical abortion when mifepristone is not available include regimens with methotrexate/misoprostol and misoprostol alone. The antifolate methotrexate provides another medical approach to pregnancy termination, but takes longer than the technique using mifepristone/misoprostol (340). Medical abortion can be induced with misoprostol alone, although it is less effective than the mifepristone/misoprostol combination. Vaginal misoprostol, 800 μg, repeated in 24 hours if fetal expulsion has not occurred, produces a complete abortion in 91% of pregnancies up to 56 days of amenorrhea (341). Complications of Medical Abortion


Gynecology_Novak

Gynecology_Novak. Heavy or prolonged bleeding is the principal complication, with up to 8% of women experiencing some bleeding for as long as 30 days. Need for surgical curettage is predicted by the gestational age when the mifepristone is administered. Two percent of women treated at 49 days or less, 3% of those treated at 50 to 56 days, and 5% of those treated at 57 to 63 days needed curettage for bleeding or failed abortion in a large study with 200 mg of mifepristone and 800 μg of vaginal misoprostol (342). Late bleeding, at 3 to 5 weeks after expulsion of the pregnancy, accounted for more than half of the curettages. The complications reported to the manufacturer of mifepristone from the first 80,000 patients treated were published (343). One woman died of ectopic pregnancy after refusing care. Another patient survived severe sepsis, and another, a 21-year-old woman with no risk factors, survived an acute myocardial infarction. Other severe sepsis cases have since occurred. A 27-year-old woman


Gynecology_Novak

Gynecology_Novak. patient survived severe sepsis, and another, a 21-year-old woman with no risk factors, survived an acute myocardial infarction. Other severe sepsis cases have since occurred. A 27-year-old woman participating in a clinical trial in Canada died of multiple organ system failure from Clostridium sordelli sepsis after complete expulsion of a 5.5-week pregnancy despite receiving excellent care (344). Five other similar sepsis deaths were reported in the popular press. The five deaths in the United States occurred among approximately 500,000 women treated with mifepristone/misoprostol, allowing estimation of a case fatality rate of 1 per 100,000, comparable to the rate of death with surgical abortion and much less than the risk of childbirth (345). There were no further cases of clostridial sepsis among the large number of women treated in the Planned Parenthood clinics when the new protocol of buccal misoprostol plus routine antibiotic prophylaxis was followed (337).


Gynecology_Novak

Gynecology_Novak. Abortions performed after 13 weeks include those done because of fetal defects, medical illness, or psychiatric problems that had not manifested earlier in pregnancy, and changed social circumstances, such as abandonment by the father. Young maternal age is the single greatest factor determining the need for late abortion (317).


Gynecology_Novak

Gynecology_Novak. Dilation and Evacuation D&E is the most commonly used method of midtrimester abortion in the United States. Typically, the cervix is prepared by insertion of hygroscopic dilators, stems of the seaweed Laminaria japonicum (laminaria), or Dilapan-S hydrophilic polymer rods. Placed in the cervical canal as small sticks, these devices take up water from the cervix and swell, triggering dilation. Laminaria, in addition, induces endogenous prostaglandin synthesis, which aids in cervical softening. When the dilators are removed the following day, sufficient cervical dilation is accomplished to allow insertion of strong forceps and a large-bore vacuum cannula to extract the fetus and placenta (346,348). Ultrasound guidance during the procedure is helpful (348). For more advanced procedures, dilators are inserted sequentially over 2 or more days to achieve a greater degree of cervical dilation (349). At the end of the midtrimester, procedures that combine serial cervical dilation with


Gynecology_Novak

Gynecology_Novak. dilators are inserted sequentially over 2 or more days to achieve a greater degree of cervical dilation (349). At the end of the midtrimester, procedures that combine serial cervical dilation with feticidal injections, induction of labor, and assisted expulsion of the fetus are used (350). Pretreatment for a few hours with buccal or vaginal misoprostol provides sufficient cervical softening and dilatation for early midtrimester D&E, and there is considerable interest in using this as an alternative to overnight laminaria further into the midtrimester (351).


Gynecology_Novak

Gynecology_Novak. Intact D&E is another modification useful for procedures at the end of the midtrimester. After wide cervical dilatation is achieved with serial placement of cervical dilators, the membranes are ruptured and an assisted breech delivery is performed, with decompression of the after-coming fetal head to allow delivery of the fetus intact (352).


Gynecology_Novak

Gynecology_Novak. In response to the federal abortion ban of 2003, an increasing number of providers are using feticidal agents prior to late second trimester terminations (353). Intra-amniotic or intrafetal digoxin and intracardiac potassium chloride are the two most common agents used for this purpose. Both are efficacious with little maternal adverse effects (354,355). The clinical utility of these agents is unproven. The only randomized controlled study looking at clinical outcomes found no change in procedure time or blood loss with the use of digoxin (356). Varying doses of digoxin were reported. In one study, 1.5 mg intra-amniotic digoxin was always successful in inducing fetal demise within 24 hours (357).


Gynecology_Novak

Gynecology_Novak. Labor-Induction Methods In Europe and the United Kingdom labor induction is much more common than D&E for midtrimester abortion (358). Induction abortion with hypertonic saline or urea was widely employed for labor induction abortion in the 1970s. These were supplanted by the use of synthetic prostaglandins, and by regimens that combine mifepristone and misoprostol.


Gynecology_Novak

Gynecology_Novak. Prostaglandins Prostaglandins of the E and F series can cause uterine contraction at any stage of gestation. The 15 methyl analogues of prostaglandin F2α (carboprost) and prostaglandin E2 (dinoprostone) are highly effective for midtrimester abortion but frequently produce side effects of vomiting, diarrhea, and with dinoprostone, fever. Misoprostol a 15 methyl analogue of PGE1, is much less expensive than other prostaglandins, stable at room temperature, and at doses effective for abortion, produces many fewer side effects (359). Transient fetal survival is not infrequent after prostaglandin inductions. In the United States, it is common to produce fetal demise before induction with regimens similar to those used in late second trimester dilation and evacuation:. intra-amniotic or intrafetal digoxin, 1 to 1.5 mg, or fetal intracardiac potassium chloride (3 mL of a 2-mmol solution).


Gynecology_Novak

Gynecology_Novak. Midtrimester Mifepristone/Misoprostol Mifepristone pretreatment markedly increases the abortifacient efficacy of gemeprost and misprostol. The mean interval from start of the prostaglandin to fetal expulsion is reduced to 6 to 9 hours, much shorter than with misoprostol alone (360). Mifepristone, 200 mg, is just as effective for this purpose as 600 mg (361). A common protocol was developed using mifepristone and misoprostol that is now recommended both by the Royal College of Obstetricians and Gynecologists (RCOG) and the World Health Organization (WHO) (358,362). Most women are cared for as hospital day-patients without need for overnight admission, a marked improvement over the labor induction methods of the past that often required 2 to 3 days of hospitalization. The protocol involves giving 200 mg of mifepristone orally on day 1. The patient returns 36 to 48 hours later for completion of the abortion with misoprostol. She is given 800 μg vaginally, and then 3 hours later, 400


Gynecology_Novak

Gynecology_Novak. giving 200 mg of mifepristone orally on day 1. The patient returns 36 to 48 hours later for completion of the abortion with misoprostol. She is given 800 μg vaginally, and then 3 hours later, 400 μgisgiven orally and repeated at 3 hour intervals up to four doses. Efficacy is greater when the interval from mifepristone to starting misoprostol is at least 36 to 38 hours (363). Mean times from the start of misoprostol to fetal expulsion are 5.9 to 6.6 hours (358,360). The RCOG mandates that legal abortion must not be allowed to terminate in a live birth. Use of a feticide is required at 21 weeks (364). In the series by Ashok et al. of 1,002 women treated with the mifepristone/misoprostol protocol, described above, patients who had not expelled the fetus after 24 hours from start of the misoprostol were given an additional dose of 200 mg mifepristone at midnight, then started on another course of five doses of misoprostol the next morning, 800 μg initially, then 400 μg at 3 hour


Gynecology_Novak

Gynecology_Novak. the misoprostol were given an additional dose of 200 mg mifepristone at midnight, then started on another course of five doses of misoprostol the next morning, 800 μg initially, then 400 μg at 3 hour intervals, all given vaginally (360). About 8% needed a curettage procedure for retained placenta. Hemorrhage requiring transfusion occurred in about 1% of patients, usually from retained placenta.


Gynecology_Novak

Gynecology_Novak. Combination of Induction Hern developed a procedure that combines a feticidal injection of digoxin with serial insertion and Assisted Delivery of multiple laminaria tents over 2 to 3 days, followed by amniotomy, placement of misoprostol in the lower uterine segment, and intravenous oxytocin to induce labor, and then an assisted delivery (365). The procedure was successful in a large case series at 18 to 34 weeks with very few complications. High-Dose Oxytocin Oxytocin in very high doses is as effective as dinoprostone at 17 to 24 weeks of pregnancy, but is not equal to the mifepristone/misoprostol regimen described above (365). Patients initially receive an infusion of 50 U of oxytocin in 500 mL of 5% dextrose and normal saline over 3 hours; 1 hour of no oxytocin, followed by a 100-U, 500-mL solution over 3 hours; another hour of rest; and then a 150-U, 500-mL solution over 3 hours, alternating 3 hours of oxytocin


Gynecology_Novak

Gynecology_Novak. Table 10.11 Complications of 2,935 Midtrimester Dilation and Evacuation Abortion and Intervention Rates on a Referral Service From Frick AC, Drey EA, Diedrich JT, et al. Effect of prior cesarean delivery on risk of second-trimester surgical abortion complications. Obstet Gynecol 2010;115:762 [Table 2], with permission. with 1 hour of rest. The oxytocin is increased by 50 U in each successive period, until a final concentration of 300 U in 500 mg. Complications of Second Trimester Abortion


Gynecology_Novak

Gynecology_Novak. Complications of second trimester surgical abortion are uncommon, but risk increases with gestational age. Complications and their frequency encountered in almost 3,000 midtrimester abortions performed by laminaria followed by D&E on a referral service are listed in Table 10.11. The gestational ages were 14 to 27 weeks and mean gestational age was 20.2 weeks. The most common complication was a cervical laceration that required suturing. A major complication, defined as one necessitating transfusion, disseminated intravascular coagulation, reoperations with uterine artery embolization, laparoscopy, or laparotomy, was encountered in 1.3% of patients. History of two or more cesareans, gestational period of 20 weeks or more, and insufficient initial cervical dilation by laminaria were independent risk factors for a major complication in a multivariate analysis (366). The rates of complication in Table 10.11 cannot be directly compared to the rates of complications with labor-induction


Gynecology_Novak

Gynecology_Novak. risk factors for a major complication in a multivariate analysis (366). The rates of complication in Table 10.11 cannot be directly compared to the rates of complications with labor-induction abortion described below because half of the D&E group were 20 weeks or more gestation, while only a few of the induction patients were more than 20 weeks.


Gynecology_Novak

Gynecology_Novak. The labor-induction methods share common hazards: failure of the primary procedure to produce abortion within a reasonable time, incomplete abortion, retained placenta, hemorrhage, infection, and embolic phenomena. With modern protocols, these are rare. In a series of 1,002 women treated with mifepristone and misoprostol at 13 to 21 weeks, 0.7% required a blood transfusion, 0.3% required ergot treatment for hemorrhage, and one required laparotomy for otherwise uncontrollable hemorrhage; 2.6% of patients received antibiotics for presumed pelvic infection after hospital discharge and 7.9% complained of prolonged bleeding (360). Uterine rupture was reported in women with previous cesarean delivery treated with misoprostol in the midtrimester, but in a case series of 101 women with one or more previous cesarean births and three smaller case series totaling 87 patients, no ruptures occurred (367). Larger series are needed to quantify the risk.


Gynecology_Novak

Gynecology_Novak. Selective Fetal Reduction Multifetal pregnancies are at risk for extremely preterm birth and major neonatal complications. To prevent this, selective reduction of higher-order multiple gestations often is practiced. The largest series describes 3,513 pregnancies treated with ultrasound-guided fetal intracardiac injection of potassium chloride (0.2–0.4 mL of a 2-mmol solution in the first trimester, 0.5–3.0 mL in the second trimester). The rate of fetal loss fell as operators gained experience. Loss was greater with higher starting number of gestations (starting number greater than six, 15.4% loss, decreasing to 6.2% loss for starting number of two gestations), and greater if more fetuses were left intact (finishing number three, 18.4% loss, decreasing to 7.6% for finishing number of gestations of one) (368). Another indication for selective reduction is the presence of one anomalous fetus in a multifetal gestation. In a series of 402 patients treated for this indication, rates of


Gynecology_Novak

Gynecology_Novak. of one) (368). Another indication for selective reduction is the presence of one anomalous fetus in a multifetal gestation. In a series of 402 patients treated for this indication, rates of pregnancy loss after the procedure by gestational age at the time of procedure were 5.4% at 9 to 12 weeks, 8.7% at 13 to 18 weeks, 6.8% at 19 to 24 weeks, and 9.1% at 25 weeks or more (369). No maternal coagulopathy occurred, and no ischemic damages or coagulopathies were seen in the surviving neonates. Maternal serum α-fetoprotein remains elevated into the second trimester after first-trimester procedures (370). Because of the possibility of embolic phenomena and infarction in the surviving twin, a different technique is needed for selective reduction of monoamniotic twins or with monochorionic twin–twin transfusion syndrome. He and colleagues describe ultrasound guided bipolar coagulation of the umbilical cord of the affected twin in such cases (371).


Gynecology_Novak

Gynecology_Novak. The Future Spermicides Research includes efforts to develop spermicides and microbicides that prevent pregnancy and are effective against HIV and STDs. Trials of microbicides such as cellulose sulphate and surfactant were disappointing and showed no efficacy against HIV (371,372). The most promising research includes development of antiretroviral microbicides with alternative delivery systems such as rings and gels. The antiretroviral tenofovir has good safety and efficacy in animals and human tissue models and is being evaluated in human effectiveness studies (373). Intrauterine Devices The GyneFix, a frameless copper IUD available in Europe, consists of a surgical suture with small copper cylinders crimped to it. The knot on the proximal end of the suture is pushed 1 cm into the uterine wall with a special inserter. Comparative trials found it more effective than the copper T380A and it requires fewer removals for pain and bleeding (374).


Gynecology_Novak

Gynecology_Novak. Other ongoing research of IUDs includes a smaller levonorgestrel IUD that may be more acceptable to nulliparous women and IUDs that are suitable for irregularly shaped uteri (38). Vaginal Rings Silastic vaginal rings releasing either progestin or progestin–estrogen combinations were studied for years. The NuvaRing contains both estrogen and progestin, must be changed monthly, and has the same safety concerns as the other estrogen-containing hormonal methods. A new reusable ring, Nestorone, contains a nonandrogenic progestin that is inactive orally, and ethinyl estradiol. It can be worn for 3 weeks, removed for 1 week, and then reinserted for a total of 13 months of use (375). The advantage of this method is the use of a less androgenic progestin and the elimination of regular trips to the pharmacy. Progering contains natural progesterone and no estrogen. It is approved in some countries in Latin America and Asia. It was developed for up to 3 months use by breastfeeding women (376).


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Gynecology_Novak. Barrier Methods The Ovaprene ring is a nonhormonal “one-size-fits-all” intravaginal organic silicone ring that continuously releases spermiostatic and spermicidal agents over a 4-week period. The phase I trial demonstrated patient acceptability and safety and the product is in phase II trials (377). Under investigation is the SILCS diaphragm, a single-size reusable device with a contoured rim. This device is nonlatex and is available over the counter with no requirement for a pelvic examination (378). Another potential new barrier method under development is a female condom with a dissolvable capsule to ease insertion, a polyurethane vaginal pouch, and a soft outer ring. Fit and concerns over slippage are improved by urethane foam that allows the condom to cling to the vaginal walls (38).


Gynecology_Novak

Gynecology_Novak. Fit and concerns over slippage are improved by urethane foam that allows the condom to cling to the vaginal walls (38). The Invisible Condom™ is a novel barrier/germicide/spermicide combination in human trials. It is a polymer gel that adheres to the vaginal and cervical mucosa when inserted into the vagina through a special applicator, forming a nondetectable physical barrier. One version has sodium laurel sulfate (SLS) incorporated in to the polymer film. The gel by itself blocks entry of HIV and of herpes virus into target cells in vitro. Daily vaginal application of the polymer plus SLS prevents pregnancy in rabbits (379).


Gynecology_Novak

Gynecology_Novak. Contraceptive Vaccines Immunologic contraception–sterilization with vaccination against human chorionic gonadotropin was pursued for many years in India but appears to be abandoned (380). Zona pellucida glycoproteins are another target for a potential vaccine, but application in humans appears blocked by the ovarian dysfunction observed in animal studies (381). More promising are efforts that target sperm. Because of the large number of antigens associated with sperm, some of which are found on somatic cells, the challenge lies in choosing the correct antigen (382). The search continues for target proteins unique to reproduction to which a vaccine could be employed without adversely affecting other functions.


Gynecology_Novak

Gynecology_Novak. Male Contraception As described earlier, considerable progress was made in hormonal contraception for men based on long-acting androgens in combination with progestins or GnRH antagonists. Nonhormonal male methods are being investigated. These include efforts to target and specifically interfere with spermatogenesis, epididymal sperm maturation, and sperm function (383). The majority of the targets being explored involve inhibiting sperm motility (384). Chinese researchers developed a method of percutaneous occlusion of the vas that was used in more than 100,000 men; it is effective and appears to be reversible. Polyurethane elastomer is injected into the vas, where it solidifies and forms a plug, providing an effective block to sperm. The plugs are removed using local anesthesia, and fertility returns in most cases after as long as 4 years with the plugs in situ (385).


Gynecology_Novak

Gynecology_Novak. Another potentially reversible method is the reversible inhibition of sperm under guidance (RISUG). This is a clear polymer gel mixed with dimethyl sulphoxide that solidifies, causing partial obstruction and the rupture of passing sperm membranes, when injected into the vas. Phase II trials demonstrated azoospermia for at least 1 year (38).


Gynecology_Novak

Gynecology_Novak. Another critical area for contraceptive development is nonsurgical means of sterilization of both men and women. Intrauterine quinacrine is the most promising method for nonsurgical female sterilization, but the method is embroiled in controversy because it was developed in the third world and moved quickly to widespread use without adequate proof of safety (386). Approximately 100,000 women were treated with it (387). The technique is very simple: pellets containing 252 mg of quinacrine are inserted into the uterus through an IUD inserter during the proliferative phase of the cycle and again 1 month later. Intrauterine quinacrine produces sclerosis of the proximal fallopian tube. In a large trial in Vietnam, the cumulative pregnancy rate for 1,335 women who received 2 doses was 3.3 at 1 year, 10.0 at 5 years, and 12.1 at 10 years (388). Another study of almost 25,000 women found the rate of ectopic pregnancy to be 0.26 per 1,000 women treated, which was similar to surgical


Gynecology_Novak

Gynecology_Novak. 3.3 at 1 year, 10.0 at 5 years, and 12.1 at 10 years (388). Another study of almost 25,000 women found the rate of ectopic pregnancy to be 0.26 per 1,000 women treated, which was similar to surgical sterilization and the IUD, OC pills, and condoms (0.42–0.45 per 1,000) and less than nonusers of contraception (1.18 per 1,000) (389). Concern was raised that quinacrine would lead to reproductive tract cancers. Two epidemiologic studies found no apparent increased risk for cancer from previous quinacrine sterilization in humans (390,391). A study of lifetime risk in rats sterilized with intrauterine quinacrine as young adults did find an increase in reproductive tract cancer in those rats treated with eight times the human dose, but not in the rats exposed to lower doses (392).


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Gynecology_Novak. 1. Haymes, NE. Medical history of contraception. New York: Gamut traceptive choice: a literature update: part I. Fam Plann Perspect Press, 1963. 1992;24:75–84. 2. Central Intelligence Agency. The world factbook. https://www.cia. 4. Mosher WD, Jones J. Use of contraception in the United States gov/library/publication/the-world-factbook/geos/xx.html. 1982–2008. National Survey of Family Growth. Vital Health Stat 3. Cates W Jr. Family planning, sexually transmitted diseases and con-2010;23:1–44. 5. Jones RK, Darroch JE, Henshaw SK. Patterns in the socioeconomic characteristics of women obtaining abortions in 2000–2001. Perspect Sex Reprod Health 2002;34:226–235. 6. Ory, HW. Mortality associated with fertility and fertility control: 1983. Fam Plann Perspect 1983;15:57–63. 7. Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010;59:1–86. 8.


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Gynecology_Novak. 7. Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR 2010;59:1–86. 8. Ashraf, T, Arnold SB, Maxfield, M. Cost effectiveness of levonorgestrel subdermal implants: comparison with other contraceptive methods available in the United States. J Reprod Med 1994;39:791– 798. 9. Brown A. Long-term contraceptives. Best Pract Res Clin Obstet Gynaecol 2010;24:617–631. 10. Grimes DA. Forgettable contraception. Contraception 2009;80:497– 499. 11. Potts M. Coitus interruptus. In: Corson SL, Derman RJ, Tyrer L, eds. Fertility control. Boston, MA: Little, Brown, 1985:299–306. 12. DiVincenzi, I (for the European Study Group). A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. N Engl J Med 1994;331:341–346. 13. Jones RK, Fennell J, Higgins JA, et al. Better than nothing or savvy risk-reduction practice? The importance of withdrawal. Contraception 2009;79:407–410. 14.


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Gynecology_Novak. 13. Jones RK, Fennell J, Higgins JA, et al. Better than nothing or savvy risk-reduction practice? The importance of withdrawal. Contraception 2009;79:407–410. 14. McNeilly AS. Suckling and the control of gonadotropin secretion. In: Kenobi E, Neil JD, Ewing LI, et al., eds. The physiology of reproduction. New York: Raven Press, 1988:2323–2349. 15. Short RV, Lewis PR, Renfree, MB, et al. Contraceptive effects of extended lactational amenorrhoea: beyond the Bellagio Consensus. Lancet 1991:337:715–717. 16. Queenan JT. Contraception and breast feeding. Clin Obstet Gynecol 2004;47:734–739. 17. Van der Wijden C, Kleijnen J, Van den Berk T. Lactational amenorrhea for family planning. Cochrane Database Syst Rev 2003;4:CD001329. 18. Lee SY, Kim MT, Kim SW, et al. Effect of lifetime lactation on breast cancer risk: a Korean women’s cohort study. Int J Cancer 2003;105:390–393. 19.


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Gynecology_Novak. 18. Lee SY, Kim MT, Kim SW, et al. Effect of lifetime lactation on breast cancer risk: a Korean women’s cohort study. Int J Cancer 2003;105:390–393. 19. American College of Obstetricians and Gynecologists. Special Report from ACOG. Breastfeeding: maternal and infant aspects. ACOG Clinical Review 2009;12: Supp. 1S-15S. 20. Genuis SJ, Bouchard TP. High-tech family planning: reproductive regulation through computerized fertility monitoring. Eur J Obstet Gynecol Reprod Biol 2010;153:124–130. 21. Fehring RJ, Schneider M, Barron ML, et al. Cohort comparison of two fertility awareness methods of family planning. J Reprod Med 2009;54:165–170. 22. Russell, J, Grummer-Strawn, L. Contraceptive failure of the ovulation method of periodic abstinence. Fam Plann Perspect 1990;22: 65–75. 23. Che, Y, Cleland JG, Ali MM. Periodic abstinence in developing countries: an assessment of failure rates and consequences. Contraception 2004;69:15–21. 24.


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Gynecology_Novak. 23. Che, Y, Cleland JG, Ali MM. Periodic abstinence in developing countries: an assessment of failure rates and consequences. Contraception 2004;69:15–21. 24. Guerrero R, Rojas OI. Spontaneous abortion and aging of human ova and spermatozoa. N Engl J Med 1975;293. 25. Gallo MF. Non-latex versus latex male condoms for contraception. Cochrane Database Syst Rev 2003;2:CD003550. 26. Grady, WR, Tanfer, K. Condom breakage and slippage among men in the United States. Fam Plann Perspect 1994;26:107–112. 27. Voeller B, Coulson AH, Bernstein GS, et al. Mineral oil lubricant causes rapid deterioration of latex condoms. Contraception 1989;39:95–102. 28. Stone KM, Grimes DA, Magder LS. Personal protection against sexually transmitted diseases. Am J Obstet Gynecol 1986;155:180– 188. 29. Kelaghan J, Rubin GL, Ory HW, et al. Barrier-method contraceptives and pelvic inﬂammatory disease. JAMA 1982;248:184–187. 30.


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Gynecology_Novak. 29. Kelaghan J, Rubin GL, Ory HW, et al. Barrier-method contraceptives and pelvic inﬂammatory disease. JAMA 1982;248:184–187. 30. Cramer DW, Goldman MB, Schiff I, et al. The relationship of tubal infertility to barrier method and oral contraceptive use. JAMA 1987;257:2246–2250. 31. Judson FN, Ehret JM, Bodin GF, et al. In vitro evaluations of condoms with and without nonoxynol 9 as physical and chemical barrier against Chlamydia trachomatis, herpes simplex virus type 2 and human immunodeficiency virus. Sex Transm Dis 1989;16: 251–256. 32. Fischl MA, Dickinson GM, Scott GB, et al. Evaluation of heterosexual partners, children, and household contacts of adults with AIDS. JAMA 1987;257:640–644. 33. deVincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med 1994;331:341– 346. 34.


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Gynecology_Novak. 34. Hira SK, Feldblum PJ, Kamanga J, et al. Condom and nonoxynol9 use and the incidence of HIV infection in serodiscordant couples in Zambia. Int J STI AIDS 1997;8:243–250. 35. Wilkinson D, Ramjee G, Tholandi M, et al. Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections by women from men. Cochrane Database Syst Rev 2002;4:CD003939. 36. Harris RW, Brinton LA, Cowdell RH, et al. Characteristics of women with dysplasia or carcinoma in situ of the cervix uteri. Br J Cancer 1980;42:359–369. 37. Parazzini F, Negri E, La Vecchia C, et al. Barrier methods of contraception and the risk of cervical neoplasia. Contraception 1989;40: 519–530. 38. Rowlands S. New technologies in contraception. BJOG 2009;116: 230–239. 39. Valappil T, Kelaghan J, Macaluso M, et al. Female condom and male condom failure among women at high risk for sexually transmitted disease. Sex Transm Dis 2005;32:35–43. 40.


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Gynecology_Novak. 39. Valappil T, Kelaghan J, Macaluso M, et al. Female condom and male condom failure among women at high risk for sexually transmitted disease. Sex Transm Dis 2005;32:35–43. 40. Galvao LW, Oliveira LC, Diaz J, et al. Effectiveness of female condom and male condom in preventing exposure to semen during vaginal intercourse: a randomized trial. Contraception 2005;71:130– 136. 41. Trussel J, Sturgen K, Strickler J, et al. Comparative efficacy of the female condom and other barrier methods. Fam Plann Perspect 1994;26:66–72. 42. Soper DE, Brockwell NJ, Dalton HP. Evaluation of the effects of a female condom on the female genital tract. Contraception 1991;44:21–29. 43. Wilkinson D, Tholandi M, Ramjee G, et al. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomized controlled trials including more than 5,000 women. Lancet Infect Dis 2002;2:613–617. 44.


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Gynecology_Novak. 44. Malyk B. Nonoxynol-9: evaluation of vaginal absorption in humans. Raritan, NJ: Ortho Pharmaceutical, 1983. 45. Linn S, Schoenbaum SC, Monson RR, et al. Lack of association between contraceptive usage and congenital malformation in offspring. Am J Obstet Gynecol 1983;147:923–928. 46. Harlap S, Shiono PH, Ramcharon S, et al. Chromosomal abnormalities in the Kaiser-Permanente birth defects study, with special reference to contraceptive use around the time of conception. Teratology 1985;31:381–387. 47. Hooton TM, Hillier S, Johnson C, et al. Escherichia coli bacteriuria and contraceptive method. JAMA 1991;265:64–69. 48. van der Straten A, Kang MS, Posner SF, et al. Predictors of diaphragm use as a potential sexually transmitted disease/HIV prevention method in Zimbabwe. Sex Transm Dis 2005;32:64–71. 49. Hooton TM, Scholes D, Huges JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med 1996;335:468–474. 50.


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Gynecology_Novak. 49. Hooton TM, Scholes D, Huges JP, et al. A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med 1996;335:468–474. 50. Davis JP, Chesney J, Wand PJ, et al. Toxic shock syndrome: epidemiologic features, recurrence, risk factors and prevention. N Engl J Med 1980;303:1429–1435. 51. Shihata AA, Gollub E. Acceptability of a new intravaginal barrier contraceptive device (Femcap) Contraception 1992;46:511–519. 52. U.S. Food and Drug Administration. US FDA FemCap Physician Labeling. Available online at: www.accessdata.fda.gov/cdrh docs/ pdf2/P020041c.pdf 53. Yranski PA, Gamache ME. New options for barrier contraception. JOGNN 2008; 37:384–89. 54. U.S. Food and Drug Administration. US FDA Lea’s Shield Physician Labeling. Available online at: www.accessdata.fda.gov/ cdrh docs/pdf/P010043c.pdf 55. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive technology. New York: Ardent Media, 2004. 56.


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Gynecology_Novak. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive technology. New York: Ardent Media, 2004. 56. Borko E, McIntyre SL, Feldblum PJ. A comparative clinical trial of the contraceptive sponge and Neo Sampoon tablets. Obstet Gynecol 1985;654:511–515. 57. United Nations. World contraceptive use, 2007. New York: United Nations Publications, 2007. 58. Sivin I, Stern J. Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu 380A intrauterine contraceptive devices: a multicenter study. Fertil Steril 1994;61:70–77. 59. El Badrawi HH, Hafez ES, Barnhart MI, et al. Ultrastructural changes in human endometrium with copper and nonmedicated IUDs in utero. Fertil Steril 1981;36:41–49. 60. Umapathysivam K, Jones WR. Effects of contraceptive agents on the biochemical and protein composition of human endometrium. Contraception 1980;22:425–440. 61. Mirena Full Prescribing Information. Bayer Healthcare. Pharmaceuticals, 2009. 62.


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Gynecology_Novak. 61. Mirena Full Prescribing Information. Bayer Healthcare. Pharmaceuticals, 2009. 62. Rose S, Chaudhari A, Peterson CM. Mirena (levonorgestrel intrauterine system): successful novel drug delivery option in contraception. Adv Drug Del Rev 2009;61:808–812. 63. Stanford JB, Mikolajczyk RT. Mechanism of action of the intrauterine device: update and estimation of post fertilization effect. Am J Obstet Gynecol 2002;187:1699–1708. 64. Alvarez F, Guiloff E, Brache V, et al. New insights on the mode of action of intrauterine devices in women. Fertil Steril 1989;49:768– 773. 65. Segal S, Alvarez-Sanchez F, Adejeuwon CA, et al. Absence of chorionic gonadotropin in sera of women who use intrauterine devices. Fertil Steril 1985;44:214–218. 66. Anonymous. Long term reversible contraception. Twelve years experience with the TCU380A and TCU220C. Contraception 1997; 56:341–352. 67.


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Gynecology_Novak. 66. Anonymous. Long term reversible contraception. Twelve years experience with the TCU380A and TCU220C. Contraception 1997; 56:341–352. 67. Irvine GA, Campbell-Brown MB, Lumsden MA, et al. Randomized comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. BJOG 1998;10:592–598. 68. Magalhaes J, Aldrighi JM, de Lima GR. Uterine volume and menstrual patters in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. Contraception 2007;75:193–198. 69. Rizkalla HF, Higgins M, Kelehan P, et al. Pathological findings associated with the presence of a Mirena intrauterine system at hysterectomy. Int J Gynecol Pathol 2008;27:74–78. 70. Suhonen SP, Holmstr¨om T, Allonen HO, et al. Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy. Fertil Steril 1995;63:336–342. 71.


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Gynecology_Novak. 70. Suhonen SP, Holmstr¨om T, Allonen HO, et al. Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy. Fertil Steril 1995;63:336–342. 71. Hill DA, Weiss NS, Voigt LF, et al. Endometrial cancer in relation to intrauterine device use. Int J Cancer 1997;70:278–281. 72. Vercellini P. A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrheal associated with endometriosis: a pilot study. Fertil Steril 1999;72:505–508. 73. Fedele L. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Fertil Steril 2001;75:485– 488. 74. Sheng J, Zhang JP, Lu D. The LNG-IUS study on adenomyosis: a 3-year follow-up study on the efficacy and side effects of the use of levonorgestrel intrauterine system for the treatment of dysmenorrhea associated with adenomyosis. Contraception 2009;79:189– 193. 75.


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Gynecology_Novak. 75. Burkeman RT, for the Women’s Health Study. Association between intrauterine devices and pelvic inﬂammatory disease. Obstet Gynecol 1981;57:269–276. 76. Farley TMM, Rosenberg MJ, Rowe PJ, et al. Intrauterine devices and pelvic inﬂammatory disease: an international perspective. Lancet 1992;339:785–788. 77. Lee NC, Rubin GL, Borucki R. The intrauterine device and pelvic inﬂammatory disease revisited: new results from the Women’s Health Study. Obstet Gynecol 1988;72:721–726. 78. Kriplani A, Buckshee K, Relan S, et al. Forgotten intrauterine device leading to actinomycotic pyometra, 13 years after menopause. Eur J Obstet Gynecol Reprod Biol 1994;53:215–216. 79. Westhoff C. IUDs and colonization or infection with actinomyces. Contraception 2007;75:S48–S50. 80. World Health Organization. Select practice recommendations for contraceptive use. Geneva: WHO, 2002. 81. Mol BW. Contraception and the risk of ectopic pregnancy. Contraception 1995;52:337. 82.