Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Hysterectomy, endometrial destruction, and levonorgestrel releasing intrauterine system (Mirena) for heavy menstrual bleeding: systematic review and meta-analysis of data from individual patients.

OBJECTIVE: To evaluate the relative effectiveness of hysterectomy, endometrial destruction (both "first generation" hysteroscopic and "second generation" non-hysteroscopic techniques), and the levonorgestrel releasing intrauterine system (Mirena) in the treatment of heavy menstrual bleeding. DESIGN: Meta-analysis of data from individual patients, with direct and indirect comparisons made on the primary outcome measure of patients' dissatisfaction. DATA SOURCES: Data were sought from the 30 randomised controlled trials identified after a comprehensive search of the Cochrane Library, Medline, Embase, and CINAHL databases, reference lists, and contact with experts. Raw data were available from 2814 women randomised into 17 trials (seven trials including 1359 women for first v second generation endometrial destruction; six trials including 1042 women for hysterectomy v first generation endometrial destruction; one trial including 236 women for hysterectomy v Mirena; three trials including 177 women for second generation endometrial destruction v Mirena). Eligibility criteria for selecting studies Randomised controlled trials comparing hysterectomy, first and second generation endometrial destruction, and Mirena for women with heavy menstrual bleeding unresponsive to other medical treatment. RESULTS: At around 12 months, more women were dissatisfied with outcome with first generation hysteroscopic techniques than with hysterectomy (13% v 5%; odds ratio 2.46, 95% confidence interval 1.54 to 3.9, P<0.001), but hospital stay (weighted mean difference 3.0 days, 2.9 to 3.1 days, P<0.001) and time to resumption of normal activities (5.2 days, 4.7 to 5.7 days, P<0.001) were longer for hysterectomy. Unsatisfactory outcomes were comparable with first and second generation techniques (odds ratio 1.2, 0.9 to 1.6, P=0.2), although second generation techniques were quicker (weighted mean difference 14.5 minutes, 13.7 to 15.3 minutes, P<0.001) and women recovered sooner (0.48 days, 0.20 to 0.75 days, P<0.001), with fewer procedural complications. Indirect comparison suggested more unsatisfactory outcomes with second generation techniques than with hysterectomy (11% v 5%; odds ratio 2.3, 1.3 to 4.2, P=0.006). Similar estimates were seen when Mirena was indirectly compared with hysterectomy (17% v 5%; odds ratio 2.2, 0.9 to 5.3, P=0.07), although this comparison lacked power because of the limited amount of data available for analysis. CONCLUSIONS: More women are dissatisfied after endometrial destruction than after hysterectomy. Dissatisfaction rates are low after all treatments, and hysterectomy is associated with increased length of stay in hospital and a longer recovery period. Definitive evidence on effectiveness of Mirena compared with more invasive procedures is lacking.

Survey of laparoscopic entry injuries provoking litigation.

STUDY OBJECTIVE: To examine injuries sustained during laparoscopic entry procedures that provoked malpractice claims in order to discern relative vulnerability of specific organs and differences in injury patterns, mortality, and financial awards, and specific entry devices involved in domestic claims versus those in other countries. DESIGN: Survey (Canadian Task Force classification II-2). SETTING: Insurance company records. INTERVENTIONS: Abstracts of malpractice allegations in 135 domestic cases insured by United States member companies of the Physician Insurers Association of America and 111 cases by its non-United States affiliates were examined. MEASUREMENTS AND MAIN RESULTS: Most cases in the United States involved biliary-gastrointestinal surgery rather than gynecologic procedures; this was reversed for the non-United States database. Major vessel injury was proportionally more common in the domestic group. Small bowel led the group of structures injured. Most injuries involved trocars of various types (185), including blunt types (16); and needle injuries were noted in 39 cases. Injuries were recognized more immediately in the United States, and mortality was related to delay in diagnosis of bowel penetration. Indemnity payments were greater for serious nonfatal injuries versus deaths in the United States, but the opposite was true in other countries. CONCLUSION: Probably no needle-trocar system can guarantee avoidance of injury during laparoscopic entry, especially when the trajectory of insertion puts great vessels at risk. Bowel injuries occur during open as well as closed techniques of insertion, and with optical trocar systems as well. Vascular injury is usually obvious, but delayed recognition of loss of bowel integrity is related to increased mortality, especially in patients over 60 years of age.

A multicenter evaluation of endometrial ablation by Hydro ThermAblator and rollerball for treatment of menorrhagia.

STUDY OBJECTIVE: To compare results of endometrial ablation using the Hydro ThermAblator (HTA) and rollerball. DESIGN: Prospective, randomized study (Canadian Task Force classification I). SETTING: Nine private practice and university centers in the United States. PATIENTS: Two hundred seventy-six women with menorrhagia due to benign causes. INTERVENTION: Endometrial ablation with the HTA (187 women) or rollerball (89). MEASUREMENTS AND MAIN RESULTS: Menstrual diaries were kept for 2 weeks and 3, 6, and 12 months after treatment. Reduction in diary scores to 75 or lower at 12 months was considered a success. For patients treated and followed according to protocol, success rates were 77% for HTA and 82% for rollerball. Amenorrhea rates at 12 months were 40% and 51%, respectively. CONCLUSION: Endometrial ablation with the HTA is safe and effective. It offers an advantage over rollerball ablation of being an office-based procedure, which reduces anesthesia requirements and obviates problems of fluid absorption.

Female reproductive endocrinology at the turn of the millennium.

The mainstays of female reproductive endocrinology, even as the millennium occurs and we cite highly technological advances in assisted reproduction, continue to be-as for the past decade-and-a-half-the use of GnRH analogs, both agonists and antagonists; the use of other gonadotropins, both alone and in combination, as well as with other types of drugs; testing for "ovarian reserve," as we attempt infertility treatment for populations that now include more nulliparous women of older reproductive age; and diagnosing and treating polycystic ovarian syndrome (PCOS), for both its reproductive and general health effects, especially as concerns insulin resistance. These topics are covered in detail, with reviews of well-controlled, and sometimes contrasting, studies.

Three spectra of laparoscopic entry access injuries.

BACKGROUND: Procedure-based surveys oflaparoscopic entry access injuries show a reassuringly low incidence, varying from 5 per 10,000 to 3 per 1,000, and, consequently, can provide only limited specific injury data. The current study uses existing injury-based reporting systems to access a uniquely large number of entry injuries to define the nature and outcomes of such events. STUDY DESIGN: Claims arising from US and non-US entry access injuries, between 1980 and 1999, reported to the Physicians Insurers Association of America by their member and affiliate companies and entry-injury medical device reports to the US FDA, from 1995 through October 1997, were analyzed to determine operative procedures, physician specialties, entry devices, and techniques associated with specific injuries. Individual injuries were analyzed for their relative incidence and potential to cause disability and death. RESULTS: Five hundred ninety-four structures or organs were injured in 506 patients, resulting in 65 deaths (13%). General surgical procedures made up at least 67% of combined medical device reports and US Physicians Insurers Association of America cases, and gynecologic procedures accounted for 63% of non-US claims. Bowel and retroperitoneal vascular injuries comprised 76% of all injuries incurred in the process of establishing a primary port. Nearly 50% of both small and large bowel injuries were unrecognized for 24 hours or longer. Delayed recognition, along with age greater than 59 years and major visceral vascular injuries, were each independent significant predictors of death. CONCLUSIONS: No entry technique or device is absolutely safe. Avoidance of entry injuries depends on patient-specific anatomic orientation and control of entry axial force. Certain entry devices can be facilitating in controlling axial force. Overall, this large aggregate of entry access injuries shows them to be more serious and, along with other data, implies that they might be more common than reported in procedure-based studies.

Evaluation of the subfertile couple: the fine points.

The basic fertility evaluation depends more on the history than findings at the initial visit. The previous reproductive history of both partners, the duration of infertility in this union, frequency of coitus, and a complete menstrual history often point to the diagnosis and correct therapy. Previous medical records pertaining to the problem are another source of information, and recent studies such as semen analysis results, ultrasound and salpingographic reports should be sought; the actual films are preferable to the reports. Previous surgeries, thought to be unrelated to fertility, may have been performed--try to get the operative report. There are myriad drugs that can interfere with fertility in either gender; therefore, a thorough history of past and present use as well as environmental toxin exposure is necessary. Often the routine prenatal tests for titers against common viral illnesses which can cause fetal damage have not been performed. Specific ethnic groups will need special testing. No invasive test or therapy should be performed on the female partner in the absence of a recent semen analysis. Ovulation evaluation can take the form of a basal body temperature chart; it's free, doesn't hurt, and is accurate in detecting the presence of ovulation, except for the exact timing. The over-the-counter urinary LH detection kits are highly reliable in predicting the actual day of ovulation. Serial ultrasounds to do this are not cost effective. This paper will discuss these points and the commonly performed evaluations such as salpingography and endoscopy. Specific hormonal evaluations of the amenorrheic patient and those with suspected polycystic ovarian syndrome will also be discussed.

One-year results of the vesta system for endometrial ablation.

STUDY OBJECTIVE: To compare a distensible multielectrode balloon for endometrial ablation with electrosurgical ablation performed by a combined resection-coagulation technique. DESIGN: Randomized, prospective trial (Canadian Task Force classification I). Setting. Eight centers. PATIENTS: Women with menorrhagia validated with a standardized pictorial blood loss assessment chart (PBAC), without intracavitary organic uterine disease, who failed or poorly tolerated medical therapy. Intervention. Results in 122 patients treated by Vesta and 112 treated surgically, evaluable at 1 year, were compared, with success defined as monthly blood loss of less than 80 ml and avoidance of additional therapy. MEASUREMENTS AND MAIN RESULTS: Pretreatment PBAC scores for patients treated by Vesta and resection or rollerball were 535+/-612 and 445 +/- 313, respectively; at 1 year they were 18+/-37 and 28+/-60, respectively. With PBAC below 75 as the definition of success, 86.9% of Vesta-treated patients were successful compared with 83.0% treated by rollerball or resection. Total amenorrhea, defined as no visible bleeding and no use of protective products, was 31.1% and 34. 8%, respectively. None of the outcome comparisons between treatments showed statistical difference. Complications in both groups were few and minor. Most (86.6%) Vesta procedures were carried out with paracervical block with or without intravenous sedation in an office or outpatient setting, compared with 79.7% epidural or general anesthesia for rollerball or resection. CONCLUSION: The Vesta system of endometrial ablation is equally effective and safe as classic resectoscopic methods. Potential advantages include avoidance of fluid and electrolyte disturbance associated with intravasation of distending media, and ability to perform the procedure under local anesthesia in an office setting with less total operating time.

Laparoscopy in the "normal" infertile patient: a question revisited.

STUDY OBJECTIVE: To determine the prevalence of reproductive pathology in a group of infertile women thought to be at low risk for altered pelvic anatomy. DESIGN: Retrospective chart review and follow-up (Canadian Task Force classification II-2). SETTING: Academic-affiliated, private reproductive endocrinology practice. PATIENTS: One hundred infertile women. INTERVENTION: Diagnostic and/or therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: Of 100 patients with a negative reproductive work-up up to the point of laparoscopy, 68 had pathology of reproductive significance: intrinsic tubal disease 24, peritubal adhesive disease 34, and endometriosis 43, some in combination. Laparoscopy was especially helpful in establishing treatment protocols for older women, who were referred for assisted reproductive techniques earlier than otherwise might have been the case. Women conceived after hormone therapy and after operative intervention. Although the hysterosalpingogram was read as normal in all women, tubal disease was diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2 having complete obstruction. Endometriosis stage I-II was found in 22 patients, stage III in 13, and stage IV in 6. CONCLUSION: Even in women thought to be at low risk for significant pelvic pathology affecting reproduction, the yield was high. Although some pregnancies were achieved after operative intervention, frequently laparoscopy was helpful in making a decision to go to assisted reproductive technology, particularly when infertility had been of long duration and in older women. Frequently the degree of pathology was such that a full operating suite was necessary to provide adequate instrumentation and anesthesia for operative intervention, which would not have been the case with office laparoscopy.

A modified acrosome induction test.

Many types of acrosome induction tests require special equipment and reagents that are not available to most clinicians; thus, simpler tests seem desirable. A modified acrosome induction test has been developed that uses basic reagents and a light microscope, which are available in most office settings. A hypoosmotic swelling test and a double stain (Bismark brown and rose Bengal) were combined to evaluate the viable acrosome reaction (AR) among 74 infertile men and 42 control men. The study included 34 infertile males without varicoceles, 20 with nonrepaired varicoceles and 20 with repaired varicoceles. On each test day, a specimen from a fertile donor was run as a control. The spontaneous acrosome reaction was recorded in semen before and after capacitation. The final % viable acrosome reaction equaled the capacitated value minus the spontaneous value for whole semen. The mean % viable AR among the control specimens was 16% with no values less than 10%. This mean value for controls was significantly greater than the mean % viable AR in each patient group. There were no overlaps in the 95% confidence intervals. When the study group was stratified according to normal acrosome induction tests or >10% viable AR, 30 patients had a normal test and 44 had abnormal tests. Six patients with varicoceles and an abnormal acrosome induction test had a varicocelectomy, and 2 (33%) converted their acrosome induction test to normal after at least 6 months of follow-up. Nine patients had in vitro fertilization (IVF), 3 had a poor result, and all had an abnormal acrosome induction test. Six had a good result with IVF and all 6 had a normal acrosome induction test. Thus, the acrosome induction test described in this report may be performed in any office laboratory to detect subtle male factor problems. The results may be helpful for planning IVF, intracytoplasmic sperm injection, or varicocele surgery for infertile men.

Ultrasound-guided soft catheter embryo transfers will improve pregnancy rates in in-vitro fertilization.

Attempts to improve clinical pregnancy rates after in-vitro fertilization (IVF) and embryo transfer are constantly being made. Two changes in technique of embryo transfer of potential clinical importance were evaluated over two contiguous time periods in order to observe any corresponding change in clinical pregnancy (CP) rate per transfer: (i) embryo transfer catheter; (ii) ultrasound guidance. Catheter choices were hard: Tefcat, Tom Cat, or Norfolk; or soft: Frydman or Wallace. Ultrasound visualization was considered to be excellent/good when the catheter could be followed from the cervix to the fundus by transabdominal ultrasound with retention of the embryo-containing fluid droplet; fair/poor if visualization could not document the sequence of events. Embryo transfers were performed in 518 cycles. CP rates per transfer using soft and hard catheters was 36 and 17% (P < 0.000) respectively. CP rates per transfer for transfers performed with and without ultrasound guidance were 38 and 25% (P < 0.002) respectively. A statistically significant difference was also noted when visualization ranks were compared. CP rates per transfer in all excellent/good ultrasound-guided transfers was 41.5 versus 16.7% for fair/poor transfers (P < 0.038). In conclusion, performance of embryo transfer with a soft catheter under ultrasound guidance with good visualization resulted in a significant increase in clinical pregnancy rates.

Inhibin-B as a test of ovarian reserve for infertile women.

The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values >/=45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values <45 pg/ml. For FSH >11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of

Ovarian response to gonadotrophins, optimal method for oocyte retrieval and pregnancy outcome in patients with vaginal agenesis.

The aim of this study is to characterize the ovarian response to stimulation and the optimal method of oocyte retrieval in patients with vaginal agenesis (Mayer- Rokitansky-Küster-Hauser syndrome) in a gestational carrier programme. Twelve patients underwent gonadotrophin stimulation and hormonal monitoring. Forty-nine treatment cycles were initiated; seven cycles were cancelled secondary to poor stimulation. Five patients had undergone surgical neovagina construction; seven patients had utilized vaginal dilators. Oocyte retrieval was achieved in one cycle via transvesical ultrasound, in two cycles via transabdominal ultrasound, in nine cycles via laparoscopy and in 30 cycles via transvaginal ultrasound. Ten pregnancies were achieved which included two clinical pregnancies, two biochemical pregnancies, three singleton births and three sets of twin births. A live birth rate of 45.5% was achieved per patient. Hormonal response to gonadotrophin stimulation in this population was similar to that of patients with normal pelvic anatomy. Pregnancy outcome was comparable to other patients utilizing gestational carriers within the same program (i.e. surgically absent uterus, anatomically non-functioning uterus, etc.). The surgical creation of a neovagina makes transvaginal retrieval technically more difficult than when dealing with a dilator-created vagina, and may require laparoscopy or transabdominal ultrasound for oocyte retrieval.

Interim results of the American Vesta trial of endometrial ablation.

STUDY OBJECTIVE: To compare results of endometrial ablation using the Vesta system compared with resection and rollerball. DESIGN: Multicenter, prospective, randomized, controlled study (Canadian Task Force classification I). SETTING: Private practice and academic center. PATIENTS: Women with menorrhagia documented by menstrual diaries who failed or refused hormonal therapy and who had no major uterine organic lesions. INTERVENTIONS: Vesta endometrial ablation or traditional endometrial resection and rollerball ablation. MEASUREMENTS AND MAIN RESULTS: Both groups achieved excellent control of menorrhagia. CONCLUSION: Vesta is an attractive alternative to traditional methods of endometrial ablation. (J Am Assoc Gynecol Laparosc 6(1):45-49, 1999)

The fate of cryopreserved sperm acquired during vasectomy reversals.

PURPOSE: Intraoperative sperm banking has been recommended during vasectomy reversal. These specimens are maintained as insurance for possible future intracytoplasmic sperm injection. We evaluated the fate of specimens collected intraoperatively from 48 vasectomy reversal patients. MATERIALS AND METHODS: Of 75 men 48 (64.0%) agreed to intraoperative sperm banking during vasectomy reversal. A total of 135 vials of epididymal sperm, 81 vials of testicular tissue and 13 vials of vasal sperm were cryopreserved. RESULTS: Among couples who stored sperm 10 (20.8%) voluntarily discarded the specimens within 4 months of vasectomy reversal. Specimens from 31 couples (64.5%) remain in storage. Seven couples (14.6%) have used frozen sperm for intracytoplasmic sperm injection. In 3 of these couples the men were azoospermic after surgery, 2 men had 10,000 to 15,000 sperm per ml. in the ejaculate with limited motility and 2 had 1 to 2 million sperm per ml. with limited motility. The 7 women who underwent intracytoplasmic sperm injection ranged between 37 and 39 years old, which was older than the mean age of the remaining study group (32.7 years). With intracytoplasmic sperm injection fertilization was achieved in all cases and 20 of 47 eggs (42.5%) developed into embryos. Of 7 women 4 achieved biochemical pregnancies (57.1%) and 2 (28.6%) delivered newborns with epididymal sperm. Natural pregnancy occurred in 7 of 16 vasectomy reversal couples (43.7%) who were followed at least 18 months postoperatively but the time to pregnancy averaged 1 year. CONCLUSIONS: Cryopreservation of sperm collected at vasectomy reversal is recommended for patients undergoing vasoepididymostomy or vasovasostomy. The couples who used the cryopreserved sperm for intracytoplasmic sperm injection included husbands whose postoperative ejaculate remained azoospermic or severely oligospermic and wives who were approaching 40 years old. Only a limited number of couples (14.6% of the study group) have used the cryopreserved sperm but the delivered newborn rate (28.6%) was comparable to other intracytoplasmic sperm injection data. The natural pregnancy rate after vasectomy reversal was 43.7% but the time to pregnancy after surgery was lengthy (average 1 year). These findings may be helpful for counseling couples who are planning vasectomy reversal surgery and may be considering intraoperative sperm banking.

PIP: This is a follow-up study on the cryopreserved sperm specimens acquired during vasectomy reversal. The sample was composed of 75 men from whom 48 (64%) agreed to intraoperative sperm banking during vasectomy reversal. A total of 135 vials of epididymal sperm, 81 vials of testicular tissues, and 13 vials of vassal sperm were cryopreserved. The result indicates that among the couples who stored sperm, 10 (20.8%) voluntarily discarded the specimens within 4 months of vasectomy reversal. Specimens from 31 couples (64.5%) remain in storage. 7 couples (14.6%) have used frozen sperm for intracytoplasmic sperm injection. In 3 of these couples, the men were azoospermazoic after surgery, 2 men had 10,000-15,000 sperm/ml in the ejaculate with limited motility, and 2 had 1-2 million sperm/ml with limited motility. Intracytoplasmic sperm injection fertilization was achieved in all cases and 20 of 47 eggs (42.5%) developed into embryos. Of the 7 women, 4 achieved biochemical pregnancies (57.1%) and 2 (28.6%) delivered newborns with epididymal sperm. Natural pregnancy occurred in 7 of 16 vasectomy reversal couples (43.7%), but the time to pregnancy ranged from 4-18 months with an average of 1 year. Therefore, intraoperative collection and cryopreservation of epididymal and testicular sperm are recommended during vasectomy reversal surgery.

Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17beta-estradiol and norgestimate on endometrial histology.

OBJECTIVE: To evaluate the effect of a 17beta-estradiol(E2)/norgestimate (NGM) HRT regimen, which provides constant estrogen in combination with pulsed progestin administration, on endometrial histology in healthy postmenopausal women 40 to 65 years of age who had experienced natural menopause at least 12 months before the start of the study. METHODS: A total of 1,253 postmenopausal women were randomized to receive either continuous 1 mg E2, or constant estrogen, pulsed progestin regimens of 1 mg E2/30 microg NGM, 1 mg E2/90 microg NGM, or 1 mg E2/180 microg NGM (3 days on, 3 days off) in a 12-month, multicenter, double-blind study. Endometrial biopsies were obtained pre- and post-treatment, and were evaluated by at least 2 (if required, by 3) pathologists who were blinded with respect to treatment and to each other's diagnosis. RESULTS: At the end of the study, no cases of endometrial hyperplasia were diagnosed in subjects who received E2 1 mg/NGM 90 microg or E21 mg/NGM 180 microg, whereas 74 (28%) and 16 (6%) cases of endometrial hyperplasia were diagnosed in subjects who received continuous E2 1 mg and E2 1 mg/NGM 30 microg, respectively. A dose-related endometrial response to NGM was apparent (P < .001). The percentage of patients with inactive/atrophic endometrium increased with NGM dose. CONCLUSION: The results of this study support the safety and efficacy of this unique HRT regimen and suggest that the minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E2 1 mg is 90 microg.

Achieving and maintaining pregnancy after age 40.

Demographic data from the United States show the need for testing ovarian reserve in a population that is increasingly delaying reproduction. The childless rate for U.S. women over the age of 35 has nearly doubled to 25% since 1925. Yet, in 1994 approximately one-third of all first births were by women over the age of 35. The first-line treatment for the aging effect on the ovarian reservoir of oocytes is ovulation induction. Study results reveal that a delivery rate of only 2.4% was achieved at age 42, and in 119 cycles of therapy in women above that age there were no live births. The clomiphene citrate challenge test is one method of dynamic testing of ovarian reserve. It has the advantages of simplicity and reduced cost when compared with the gonadotropic stimulatory test. In one test group utilizing the clomiphene citrate challenge test only 4.8% conceived at any age following an abnormal test. As a prognostic test with an approximate 95% accuracy rate for negative predictive value it has much to offer. With oocyte donation becoming more widespread as an acceptable method of achieving pregnancy, clomiphene citrate challenge testing should be performed more frequently, in order to spare couples the emotional and financial sequelae of multiple attempts at ovulation induction and IVF when expected pregnancy rates fall below a level acceptable to both patient and physician.

Live birth from a zygote cryopreserved for 8 years.

After a cryopreservation period of 8 years, four zygotes were thawed and transferred to the patient's uterine cavity. A singleton pregnancy resulted in the delivery of a normal male. This case report offers evidence that long terms of cryopreservation are consistent with full developmental potential post-thaw, and encourages further examination of imposing limits on length of storage of frozen concepti.