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Background: Bladder exstrophy is an uncommon anomaly rarely associated with uterus didelphys. Fertility is limited by associated vaginal malformations, which have traditionally required surgical reconstruction., Case: A woman with a history of bladder exstrophy and hypoplastic vagina presented complaining of painful intercourse. The patient underwent vaginal dilator treatment after corrective surgery for the bladder defect. Without any further fertility therapy she subsequently conceived twins, with one implantation in each horn of a didelphic uterus., Conclusion: Bladder exstrophy, uterus didelphys, and vaginal hypoplasia share a common embryological devel-opment, and the finding of one anomaly can alert to the presence of another. Vaginal dilators may be used in place of surgical reconstruction to allow conception.

Objective: To quantify the in vitro effects of gonadotropins on benign, borderline, and malignant ovarian cell lines., Design: In vitro cell culture., Setting: Research laboratory., Patient(s): None., Intervention(s): Three hormonally sensitive ovarian neoplastic cell lines were exposed to control medium, FSH (40 mIU/mL), hCG (200 mIU/mL), and a combination of FSH and hCG., Main Outcome Measure(s): Cellular proliferation measured by a colorimetric (MTT) assay., Result(s): Growth of the cell lines was similar when exposed to control or FSH. In the presence of hCG alone, the cell lines demonstrated decreased proliferation when compared to control or FSH alone. When hCG was given in combination with FSH, there was decreased proliferation of the cell lines compared to control or FSH alone., Conclusion(s): Growth of benign, borderline, and malignant ovarian epithelial cell lines is inhibited by hCG at levels, which are commonly achieved with hCG administration during ovulation induction or as a result of trophoblastic production in early pregnancy.

Objective: To assess the extent of accumulation of circulating estrone (E1), total and free estradiol (E2) and estrone sulfate (E1S) levels in postmenopausal women receiving prolonged oral E2 therapy and to determine the effect of increased estrogenicity on free testosterone levels., Study Design: Descriptive study involving 14 healthy postmenopausal women during a three-year period. Group 1 (n = 7) took a placebo. Group 2 (n = 7) took 1 mg micronized E2 daily. Blood samples were taken at one, two and three years. E2, E1 and total testosterone were quantified by radioimmunoassay (RIA) following extraction and celite chromatography. Free testosterone and E2 were calculated. Sex hormone-binding globulin (SHBG) and E1S were quantified by RIA., Results: In the control group, none of the hormone levels changed significantly. Free testosterone decreased 49% in women taking E2 replacement as compared to a 7% decline in women taking placebo. In women taking E2 replacement, E1, E2, E1S, free E2 and SHBG levels increased 10, 6, 51, 2 and 2 times, respectively, between baseline and year 3., Conclusion: E1, E2 and E1S levels significantly increased with E2 replacement. Free testosterone levels decreased with E2 replacement. Testosterone replacement may be warranted when giving postmenopausal women estrogen replacement therapy.

Objective: To establish parameters associated with successful fimbriectomy reversal and to estimate monthly fecundability and cumulative pregnancy rates through life-table analysis., Design: Series report., Setting: University-based infertility clinic., Patient(s): Forty-one women undergoing surgery for tubal sterilization reversal., Intervention(s): Surgical fimbriectomy reversal., Main Outcome Measure(s): Time from sterilization to reversal, laparoscopy vs. laparotomy, uni- vs. bilateral fimbriectomy reversal, Bruhat vs. suture, tubal lengths, postsurgical hysterosalpingogram, ovulation induction, incidence of pregnancy and outcome, and life-table analysis to determine pregnancy rate., Result(s): The mean time from sterilization to reversal was 11.5 years. Of the 41 women who underwent fimbriectomy reversal, 6 (14.6%) conceived. Sixteen reversals were performed by laparotomy resulting in 4 (25%) pregnancies, whereas 25 were performed laparoscopically resulting in 2 (8%) pregnancies. Eight had unilateral salpingostomies and 33 bilateral, of which 1 of 8 (12.5%) and 5 of 33 (15.2%) conceived, respectively. Using the Bruhat technique, 1 of 11 (9%) conceived vs. 5 of 30 (16.7%) that underwent reversal using sutures. The mean postoperative tubal length for the 6 women who conceived was 8 cm vs. 6.7 cm in the 35 women who did not conceive. Postoperatively, 26 women received ovulation induction and 1 (3.8%) conceived whereas 5 (33.3%) conceptions occurred in 15 women who did not require ovulation induction. Using life-table analysis with 619 postsurgical cycles, the monthly fecundability was.0097. The cumulative conception rate after 5 years was 31.2%., Conclusion(s): Neosalpingostomy for the reversal of fimbriectomy sterilization represents a viable option for fertility restoration. The best candidates for this procedure are spontaneously ovulatory and have a tubal length of more than 7 cm.

Purpose: To evaluate androgen production and metabolism during controlled ovarian hyperstimulation., Methods: Five women, aged 33-42, were studied. All participants were undergoing controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonist and human menopausal gonadotropins. Serum estradiol, estrone, androstenedione, testosterone, 3 alpha-androstanediol glucuronide, and sex hormone-binding globulin levels were measured at 6 time points during the cycle., Results: The levels of all steroids increased significantly from baseline during controlled ovarian hyperstimulation. Mean total testosterone levels increased from 0.29 +/- 0.05 ng/mL to 0.58 +/- 0.07 ng/mL after gonadotropin stimulation. Sex hormone-binding gonadotropin levels increased from 50 +/- 16 nM to 73 +/- 12 nM after gonadotropin stimulation. Estrone/androstenedione and estradiol/testosterone ratios, reflecting the aromatase pathway, increased whereas 3 alpha-androstanediol glucuronide/androstenedione and 3 alpha-androstanediol glucuronide/testosterone ratios, reflecting 5 alpha-reductase activity, decreased., Conclusions: Controlled ovarian hyperstimulation with human menopausal gonadotropins results in increased serum testosterone and androstenedione levels. Whereas there is an enhancement in androgen metabolism by aromatase, 5 alpha-reductase activity with regard to androgen metabolism is diminished.

Purpose: To determine prognostic significance of blastomere number on Day 3 of culture upon subsequent blastocyst (BL) development., Methods: A retrospective analysis was conducted in 37 IVF subjects undergoing standard protocols and BL transfer after sequential embryo culture in P1 and BL media., Results: Of Day 3 embryos containing 7 or more blastomeres, 68.9% (186/270) developed into BL compared to embryos containing 4-6 blastomeres, 38.1% (56/147), P < 0.0001. The majority of BL, 68.9% (168/244), were observed on Day 5. Extended Day 6 culture represented 31.1% (76/244) of all BLs., Conclusions: The observation of 7 or more blastomeres on Day 3 yielded a significantly greater likelihood of BL development. Embryos containing 4-6 blastomeres are still relatively likely to progress to a BL. Extended culture to Day 6 still yields a significant proportion of BL. Cell cleavage stage on Day 3 appears to be a useful prognostic indicator of subsequent BL development.

Objective: To determine the direction of delivery of E(2) in the female pelvis by assessing the ratio of endometrial to serum E(2) in women whose ovaries were stimulated to produce E(2) with women who received exogenous E(2)., Design: Prospective comparative study., Setting: University-based ART program., Patient(s): Oocyte donors and recipients of donor oocytes., Intervention(s): Micronized E(2) administered by the oral or vaginal route and oocyte donation., Main Outcome Measure(s): Serum and endometrial levels of E(2)., Result(s): Serum E(2) levels were significantly higher in women who underwent controlled ovarian hyperstimulation (COH) and women receiving exogenous E(2) by the vaginal route than in those who received oral E(2). Levels of E(2) in endometrial tissue were similar in women who underwent COH and those receiving oral E(2). Endometrial E(2) levels in women who underwent vaginal administration were significantly higher than those in the oral E(2) or COH groups. The ratio of endometrial to serum E(2) was highest in women who underwent vaginal E(2) and lowest in those undergoing COH., Conclusion(s): Vaginal administration of micronized E(2) results in preferential absorption of E(2) into the endometrium, consistent with a "uterine first pass" effect. Since endogenous E(2) produced the smallest ratio of E(2) between the endometrium and serum, E(2) produced by the ovaries is not preferentially delivered to the uterus.

Objective: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility., Design: Prospective randomized trial., Setting: Infertility clinic in a university teaching hospital., Patient(s): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction., Intervention(s): The women were assigned randomly to receive either TMX or CC on cycle days 5-9., Main Outcome Measure(s): Rates of ovulation and pregnancy for the two treatment modalities., Results(s): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group., Conclusion(s): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.

Objective: To compare serum estrone sulfate (E1S) levels in postmenopausal women during long-term treatment with commonly prescribed doses of oral and transdermal estradiol (E2)., Design: A retrospective study performed in a University setting in the United States involving 33 healthy postmenopausal women. Two groups of postmenopausal women were studied: group 1 (n = 10) received 1 mg oral micronized E2 daily for 16 months; blood was drawn at 0, 7, and 15 months. Group 2 (n = 23) was randomized into three subgroups. Two of the subgroups (n = 8; n = 7) received E2 delivered at a rate of 0.05 mg/day and 0.1 mg/day, respectively, by transdermal patch, changed twice weekly; the third subgroup received a placebo (without E2) patch for 9 continuous months. Blood samples were drawn at 0, 6, and 9 months. Serum E1S and E2 were quantified by specific radioimmunoassays. Statistical analysis was performed by analysis of variance., Results: After oral E2 treatment, E1S levels increased significantly (p < 0.01) from baseline, reaching an average level of 38.8 ng/mL at 15 months. After transdermal E2 treatment, E1S levels increased significantly, yet to a much lesser extent, reaching levels of 1.8 ng/mL and 3.2 ng/mL after 9 months of treatment with the 0.05 mg/day and 0.1 mg/day patches, respectively., Conclusions: Markedly elevated levels of E1S were found after long-term oral estrogen treatment. In comparison to the increase in E1S levels after long-term oral estrogen treatment, there was only a small increase in E1S levels after transdermal E2 therapy. This difference may be attributed to the higher dosage of oral E2 that is required because of the low bioavailability compared with the transdermal dosages.

Objective: This study was undertaken to determine the effect of male aging on sperm quality as determined by semen analysis, the fertilization rate of human oocytes in vitro, and live birth rates., Study Design: Retrospective analysis correlating outcome measures with male age was performed for 558 oocyte donation cycles in 441 couples. The oocyte donation model was chosen because it controls for oocyte quality and endometrial receptivity, which allows variations in sperm quality as a function of male age to be the only dependent variable. Outcome measures analyzed were semen analysis, fertilization rates in vitro, pregnancy rates, live birth rates, and cumulative live birth rates by life-table analysis., Results: There was a negative correlation between male age and total sperm count, but there was no correlation between male age and any of the other parameters in the semen analysis. There was no association between male age and the fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth rates. Recipient couples were grouped by quartiles of male age, and cumulative live birth rates were the same in the 4 groups., Conclusion: Whereas male aging is associated with a significant decline in total sperm count, this change is not reflected in a decreased fertilization rate or a decreased live birth rate in the oocyte donation model.

Objective: To determine the impact of the vaginal route of micronized estradiol (E(2)) administration upon hepatic globulin and lipid production and upon the outcome of oocyte donation cycles in which the recipients received E(2) via this route., Design: Series report., Setting: University-based assisted reproduction techniques (ART) program., Patient(s): Recipients of donor oocytes., Intervention(s): Administration of micronized E(2) via the oral or vaginal route, oocyte donation, and embryo transfer., Main Outcome Measure(s): Measurements of the serum levels of free E(2), sex hormone-binding globulin (SHBG), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), as well as endometrial thickness and pregnancy outcome., Result(s): Serum SHBG and lipoprotein levels were unaltered by the vaginal as compared with the oral route of E(2) administration. Serum free E(2) levels were significantly higher after vaginal administration. Ten patients who had previously failed to achieve adequate endometrial thickness with an oral regimen were found to have adequate endometrial thickness after vaginal E(2) administration and seven of them achieved an ongoing pregnancy after embryo transfer., Conclusion(s): Vaginal administration of micronized E(2) results in significantly higher free serum E(2) levels when compared to levels achieved after oral E(2) administration. Hepatic globulin and lipoprotein production is similar despite 10-fold higher serum E(2) levels after the vaginal administration. The greater efficiency of E(2) delivery to the endometrium after vaginal administration makes this route a good option for patients who fail to achieve adequate endometrial thickness with oral E(2) administration.

Objective: To determine the accuracy of both the hemocytometer and the MicroCell, to evaluate which method is the most reliable, and to confirm the accuracy of latex beads as an internal standard., Design: Prospective procedural assessment., Setting: University-based infertility clinic., Patient(s): One hundred sixty-five male sexual partners of women undergoing screening for infertility., Intervention(s): Semen analysis., Main Outcome Measurement(s): Sperm and latex bead concentrations., Result(s): Sperm concentration values obtained with the hemocytometer were highly correlated with those obtained from the MicroCell (r = 0.88). The mean value of the latex beads concentration was closer to the standard value using the hemocytometer than the MicroCell., Conclusion(s): Both the hemocytometer and the MicroCell are suitable as screening techniques to measure sperm concentration. Fixed suspensions of latex beads serve as reliable internal quality control standards.

Objective: To evaluate whether the presence of antiphospholipid antibodies among women undergoing IVF affects the likelihood of IVF success., Design: A meta-analysis of seven eligible studies on antiphospholipid antibodies and IVF outcome., Main Outcome Measure(s): Odds ratios (ORs) and 95% confidence intervals (CIs) of an association between the presence of antiphospholipid antibodies and both clinical pregnancy and live birth from IVF., Result(s): There was no significant association between antiphospholipid abnormalities and either clinical pregnancy (OR 0.99; 95% CI 0.64-1.53) or live birth (OR 1.07; 95% CI 0.66-1.75) in IVF patients., Conclusion(s): The measurement of antiphospholipid antibodies is not warranted in patients undergoing IVF.

Objective: Our purpose was to determine serum and endometrial estradiol levels when micronized estradiol is administered vaginally and orally., Study Design: Five subjects were given oral estradiol (2 mg twice daily), during an artificial luteal phase, and another group of 5 subjects were given the same dose of estradiol by the vaginal route. Endometrial biopsies and blood samples were obtained on day 21 of the cycle, 2 hours after the last dose was administered. Tissue and blood samples were assayed for estradiol., Results: Serum estradiol levels were significantly higher with vaginally administered estradiol than with orally administered estradiol (2344 +/- 398 vs 279 +/- 76 pg/mL, P <.005). Endometrial estradiol concentrations were also significantly higher with vaginally administered estradiol than with the oral preparation (918 +/- 412 vs 13 +/- 2 pg/mg protein, P <.05)., Conclusions: Vaginal administration of estradiol is more effective in increasing serum and endometrial levels of estradiol than the oral route and may represent the optimal route of administration for recipients of egg donation. If the vaginal route of estradiol administration is considered for menopausal replacement therapy, much lower doses of the standard oral quantities should be used. Furthermore, if the uterus is present, a progestin must be used to compensate for the high tissue levels of estradiol.

Objective: To assess plasma angiotensin-converting enzyme (ACE) activity in a patient with severe ovarian hyperstimulation syndrome (OHSS)., Design: Case report., Setting: Private, university-affiliated infertility practice., Patient(s): A 35-year-old woman with OHSS., Intervention(s): Clomiphene citrate induction of ovulation., Main Outcome Measure(s): Plasma ACE activity., Result(s): The patient had a brain stem infarction as a result of thrombosis caused by severe OHSS. Plasma ACE activity was significantly elevated and persisted long after resolution of the OHSS., Conclusion(s): Elevated ACE activity appears to have been associated with the development of OHSS in this patient. Further study of the ovarian renin-angiotensin system in the development of OHSS is warranted.

Objective: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy., Methods: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy., Results: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07)., Conclusion: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Objective: To describe retrieval of immature oocytes during unstimulated IVF and assess the in vitro maturation and fertilization rates., Design: Retrospective analysis., Setting: The USC program for assisted reproduction., Patient(s): Spontaneously ovulatory women with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor., Intervention(s): HCG administration in mid-cycle, aspiration of all visible follicles, in vitro maturation of immature oocytes in culture media versus 50% follicular fluid in media, IVF, and embryo transfer., Main Outcome Measure(s): Rates of in vitro maturation, fertilization, and implantation after embryo transfer., Result(s): A total of 101 immature oocytes were obtained during 59 follicle aspirations. Thirty percent of prophase I oocytes matured to metaphase II in vitro compared with 44% of metaphase I oocytes. Fertilization rates for matured prophase I oocytes were 62% for those cultured in standard culture media (controls) and 87% for follicular fluid culture media. Two pregnancies resulted from the transfer of embryos derived from immature oocytes when no other embryos were transferred., Conclusion(s): Immature oocytes may be retrieved successfully during the mid-cycle aspiration of the dominant follicle in unstimulated IVF cycles. Maturation of immature oocytes in vitro with follicular fluid results in similar maturation and fertilization rates as for control incubation. Immature oocytes thus retrieved contribute to the overall pregnancy success of unstimulated IVF cycles. It may be better to retrieve immature oocytes during unstimulated cycles than during the follicular phase of natural cycles.

Objective: To describe the first successful application of a new fertility-enhancing technique., Design: Case report., Setting: Academic fertility program., Patient(s): A 36-year-old nulligravid woman undergoing inseminations with frozen-thawed donor sperm., Intervention(s): Ovarian superovulation, follicle aspiration, sperm injection, and assisted follicular rupture., Main Outcome Measure(s): Assessment of feasibility of technique and pregnancy outcome., Result(s): After failing to conceive during 16 cycles of IUI, the patient successfully achieved an ongoing pregnancy during the second follicle aspiration, sperm injection, and assisted rupture (FASIAR) attempt., Conclusion(s): Follicle aspiration, sperm injection, and assisted rupture combines the concepts of superovulation, IUI, and peritoneal oocyte and sperm transfer to obviate the possibility of luteinized unruptured follicle syndrome, assist oocyte release, and ensure gamete intermixing. It also can be used to reduce the number of ovulating oocytes and thus to reduce the risk of multiple gestations. Follicle aspiration, sperm injection, and assisted rupture is a new, simple, office-based procedure that does not require embryologic expertise beyond sperm preparation as for IUI, yet promises to be more successful than IUI.

Increasing numbers of young women with ovarian failure and women of advanced reproductive age (> 40 yrs) utilize oocyte donation to treat their infertility. In both groups, women who become pregnant frequently experience multiple gestation, occurring in up to 30% of pregnancies. Advanced maternal age and high-order multiple gestations are associated with an increased risk for obstetric complications. We reviewed the pregnancies of patients with high-order multiple gestations (> or = 3 gestational sacs) with respect to their antepartum course and neonatal outcomes. Mothers were divided into two groups according to age at conception; Group I (> or = 40 yr, n = 20) and Group II (< 40 yr, n = 10). These 30 high-order multiple gestations were found among 127 successful oocyte donation cycles (23.6% of all pregnant patients). Data regarding pregnancy outcomes were gained by chart review and telephone interview. Results demonstrated spontaneous reductions in the number of implantation sites were similar between groups (Group I: 21.4% vs. Group II: 17.6%). Multifetal pregnancy reduction (MFPR) was more often chosen by older women (Group I: 45% vs. Group II: 10%; P < 0.05). Antenatal complications were commonly experienced by both groups (> 80%) as were operative deliveries (> 85%). However, neonatal outcomes were generally good, with only one death occurring in the 79 delivered infants (1.3%). We conclude transferring supernumerary embryos to women undergoing ovum donation places patients at great risk for high-order multiple gestations. These pregnancies are associated with increased antenatal and neonatal complications. Although advanced maternal age is normally an added risk factor, well-screened older patients carrying high-order multiple gestations experienced similar outcomes as younger mothers.

Objective: Our purpose was to evaluate the early luteal phase of assisted reproductive cycles utilizing controlled ovarian hyperstimulation and to compare these results with those obtained in unstimulated cycles., Study Design: We undertook a descriptive study analyzing luteal phase serum progesterone levels, endometrial histologic features, and endometrial surface ultrastructure by scanning electron microscopy of cycles utilizing controlled ovarian hyperstimulation. Study samples were obtained from 7 oocyte donors undergoing controlled ovarian hyperstimulation for the purpose of follicle aspiration in oocyte donation. Control (unstimulated) serum progesterone samples were obtained from 19 patients undergoing in vitro fertilization in unstimulated cycles. Prospective recipients of oocyte donation (n = 20) undergoing mock cycles of exogenous estradiol and progesterone acted as controls for the endometrial biopsies., Results: Serum progesterone levels on the day of human chorionic gonadotropin administration were twofold higher in the study group than in the unstimulated group (1.1 +/- 0.6 vs 0.5 +/- 0.2 ng/ml, mean +/- SD, p < 0.01). On the day of follicle aspiration, progesterone levels were much higher in the study group (8.5 +/- 2.2 vs 0.5 +/- 0.1 ng/ml, p < 0.001). Histologic dating of endometrial biopsies revealed that the study group was advanced by nearly 2 days as compared with the group having artificial cycles. Pinopods, ultrastructural markers of the implantation window, were present in only one of seven study cycles as compared with all of the four artificial cycles., Conclusions: The early luteal phase of cycles undergoing controlled ovarian hyperstimulation is characterized by markedly elevated serum progesterone levels during the periovulatory period, advanced endometrial histologic features, and an absence of endometrial pinopods at the time of embryo implantation. We speculate that these high levels of progesterone in the early luteal phase cause premature endometrial luteinization and a premature appearance of the implantation window, thus providing an explanation for the observed decrease in endometrial receptivity.

Objective: To report the occurrence of an unusual case of successful pregnancy achieved by oocyte donation in a woman > 60 years of age., Design: Case report., Setting: University-based assisted reproductive technology program., Patient(s): Sixty-three-year old nulligravida, married for 16 years to her 60-year-old husband. Throughout her infertility treatment, the patient was believed to be 10 years younger, as she claimed. She revealed her true age of 63 only upon being referred for obstetric care at 13 weeks of gestational age., Intervention(s): Oocyte donation, IVF, embryo cryopreservation, and ET., Main Outcome Measure(s): Attainment of pregnancy and subsequent delivery., Result(s): The patient underwent two cycles of oocyte donation. During the second attempt, the fresh transfer resulted in a clinical miscarriage at approximately 8 weeks of gestational age. A subsequent transfer of three frozen-thawed embryos resulted in an ongoing singleton gestation. The pregnancy was complicated by gestational diabetes (controlled by diet) and mild pregnancy-induced hypertension. Delivery by cesarean section at 38 weeks of gestational age resulted in the birth of a healthy female infant weighing 2,844 g with Apgar scores of 9 and 9., Conclusion(s): This case demonstrates that the uterus is capable of supporting nidation and subsequent gestation for many years beyond natural menopause. It shows that other aspects of human physiology are capable of adapting to the stresses and changes of pregnancy sufficiently well to achieve a normal birth at the age of 63 years. This case also exemplifies the difficulty in attempting to regulate the age of recipients in oocyte donation. As in other aspects of human life, when age limits are applied to the provision of certain services, human beings whose age falls outside of these limits become motivated to deceive the providers of those services to avail themselves of the services.

Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety of endocrinopathies and also occur in ovulatory women. By some investigators this is merely referred to as 'PCO' (polycystic ovaries). Although there is controversy in this regard, we do not consider women with PAO/PCO who have no known endocrine disturbance to have polycystic ovary syndrome (PCOS) and therefore prefer not to use the term 'PCO' which is often equated with PCOS. We studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and 15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other women were studied who were considered to have PCOS. Of these, 15 were overweight and 10 were of normal weight. All the PCOS women had serum concentrations of luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P < 0.01) than values in the normal women, regardless of ovarian morphology. These values were similar in the two groups of ovulatory women with NAO and PAO/PCO. Fasting insulin was elevated in women with PCOS with increased body weight (P < 0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in women of normal weight with PCOS. Serum insulin-like growth factor (IGF)-I and binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was significantly (P < 0.01) lower in those women with PCOS with increased body weight, compared to all other groups. Compared to values in ovulatory women with NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO and those women with PCOS of normal weight. These lower values were similar in women with PAO/PCO and in normal weight women with PCOS. On an individual basis, an elevation of at least one serum androgen value was found in 33% of women with PAO/PCO. These data confirm that increased body weight accentuates the metabolic alterations in PCOS, but suggest that subtle endocrine disturbances, similar to those that are found in PCOS, may be uncovered in up to a third of ovulatory women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is common and apparently closely associated with alterations in ovarian morphology.

Objective: To study the effect of the age of the woman who provides the oocytes or who receives the embryos on results of IVF-ET., Design: Historical cohort study. Multivariate regression analysis was used to study the age effect continuously and after adjustment for confounding., Setting: Patients of the University of Southern California, Los Angeles, California., Patient(s): Couples who underwent standard (n = 277) or donor IVF-ET (n = 294) between January 1991 and July 1995., Intervention(s): One cycle of standard or donor IVF-ET., Main Outcome Measure(s): Successive IVF outcomes from number of oocytes to ongoing pregnancy and several measures of pregnancy loss., Result(s): The number of oocytes decreased with aging of the oocyte provider. More women who received oocytes from donors aged 20 to 23 years had at least one good embryo transferred than women who received oocytes from older donors. The age of the woman who received the embryos had no effect on IVF outcomes. In women > 40 years who underwent standard IVF, the probability of pregnancy decreased. No such relationships were observed for donor IVF, but all the oocyte donors were younger., Conclusion(s): An age effect for ongoing pregnancy was only found in women > 40 years who underwent standard IVF independent of the lower number of oocytes and suggests decreasing oocyte quality.

The purpose of the present study was to determine the cumulative likelihood of pregnancy success after repetitive cycles of oocyte donation and specifically to examine the influence of recipient age and diagnosis upon the cumulative likelihood of pregnancy in an effort to identify any potential subgroup of recipients who might have diminished endometrial receptivity. We retrospectively analysed the outcome of 418 consecutive embryo transfer cycles among 276 recipients of oocyte donation in our institution. We analysed clinical pregnancy and delivery rates in the recipients divided by age groups and diagnostic groups. For the purpose of life-table analysis, only cycles prior to and including the first cycle producing a successful pregnancy were included. Frozen-thawed embryo transfers were not included in the analysis. The overall clinical pregnancy rate was 36.2% (95% CI 31-41%) and the cumulative pregnancy rate after four cycles was 87.9%. The overall delivery rate was 29.3% (95% CI 25-33%) and the cumulative delivery rate after four cycles was 86.1%. There were no statistically significant differences in any of the rates attributable to recipient age or diagnosis. No decline in per cycle success was noted over consecutive cycles. We conclude that neither recipient age nor diagnosis plays a substantial role in the success of oocyte donation, implying that endometrial receptivity is unaltered by age or diagnosis. Furthermore, up to four successive cycles of oocyte donation are associated with the same probability of success.

Objective: To evaluate what hormonal or biochemical parameters are most highly associated with the finding of polycystic-appearing ovaries as compared with normal-appearing ovaries in women with polycystic ovary syndrome (PCOS)., Design: Prospective randomized study., Setting: Academic medical center., Patients: Ten women with PCOS-five with normal-appearing ovaries and five with polycystic-appearing ovaries-were matched for age and body mass index. All had serum T levels between 80 and 150 ng/dL (conversion factor to SI unit, 3.467)., Intervention(s): Insulin infusion for the purpose of performing insulin tolerance testing to evaluate insulin resistance or sensitivity., Main Outcome Measure(s): We measured serum T, DHEAS, androstenedione, sex-hormone binding globulin, 5 alpha-androstane-3 alpha-17 beta-androstenediol glucuronide, FSH, LH, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and insulin-like growth factor binding protein-3. Insulin resistance, measured by insulin tolerance testing, also was done on the same day after the patient had fasted for at least 8 hours., Result(s): Serum androgens and binding proteins were not significantly different in both groups. Insulin tolerance testing demonstrated a slower glucose disappearance in the polycystic appearing ovary group (Kitt glucose was 4.58% +/- 1.4%/min in the normal-appearing ovaries group versus 2.07% +/- 1.07%/min in the polycystic-appearing ovaries group)., Conclusion(s): Women with PCOS and polycystic-appearing ovaries do not demonstrate any definitive serum hormonal differences compared with women with PCOS and normal-appearing ovaries. The presence of polycystic-appearing ovaries correlates significantly with the presence of insulin resistance.

Objective: To provide a descriptive analysis of the ultrastructure of the endometrial surface epithelium during the luteal phase from patients undergoing controlled ovarian hyperstimulation (COH)., Design: Prospective, observational study., Setting: Tertiary care academic IVF center., Patient(s): Twelve oocyte donors undergoing COH., Intervention(s): After oocyte aspiration, patients underwent two endometrial biopsies 2 to 7 days after hCG administration., Main Outcome Measure(s): Appearance of the endometrial epithelial surface as evaluated by scanning electron microscopy., Result(s): Endometrial maturation proceeded in an orderly manner. The ciliated cells remained unchanged, both in regards to cell density, cilia density, and ratio of ciliated cells to nonciliated cells. The microvilli became more uniformly distributed as the luteal phase progressed. The central aspect of the cells also appeared to protrude more into the endometrial lumen as the cycle progressed. Elongation the glandular orifices also was noted with progression of the luteal phase. Apical protrusions, pinopods, were noted to develop and regress during a short period during the midluteal phase spanning days 4 to 7 after hCG administration. Initial pinopod development began in the region of the glandular orifices, with substantially fewer occurring outside this region., Conclusion(s): Although the development of the endometrial ultrastructural characteristics during the luteal phase progresses in an orderly manner that is comparable to that of endometrium obtained in unstimulated cycles, pinopod expression was noted at an earlier phase of endometrial maturation. This advanced development may result in an alteration the window of implantation and affect pregnancy rates in women undergoing COH.

The importance of performing an endometrial biopsy in women preparing for oocyte donation goes beyond confirming the histologic response to hormone replacement therapy. Additional information related to uterine architecture, ease of embryo transfer, status of the ovaries, and patient compliance is also gained. Finally, the return visit provides an opportunity to discuss plans for the upcoming cycle. Whereas this report does not specifically address the question as to how many pregnancies were contingent upon the satisfactory performance of the mock cycle, we estimate that due to a combination of factors (i.e., lack of endometrial response, patient noncompliance, difficult embryo transfer), the likelihood of pregnancy in many cases would have been substantially reduced had the preliminary cycle not been attempted.

Objective: To manipulate the luteal endometrial progression by the use of antiprogestins., Design: Prospective controlled clinical trial., Setting: The IVF program of the University of Southern California School of Medicine, Los Angeles, California., Patient(s): Thirteen oocyte donors and 20 oocyte recipients., Intervention(s): Controlled ovarian hyperstimulation of oocyte donors, administration of two doses of 2.5 mg of RU486 to the study group, and endometrial biopsies., Main Outcome Measure(s): Serum E2 and P levels, histologic dating of the endometrium, endometrial ultrastructure by scanning electron microscopy., Result(s): No difference in serum E2 or P levels was noted after RU486 administration. The histologic dating was advanced in oocyte donors as compared with recipients undergoing artificial cycles but returned to normal (in phase) after RU486. Pinopods were noted in all recipient biopsies and in donors treated with RU486 but in only one of four biopsies in donor controls., Conclusion(s): Cycles with controlled ovarian hyperstimulation are associated with high early luteal P levels and advanced endometrial histology. Low doses of RU486 may correct the precocious luteinization and restore endometrial receptivity.

Purpose: To analyze the effects and potential benefits of a single midcycle dose of follicle-stimulating hormone (FSH) prior to human chorionic gonadotropin (hCG) administration during unstimulated in vitro fertilization (IVF) cycles., Methods: Twenty-five cycles from 20 patients receiving 150 IU of FSH 42-44 h and 10,000 IU of hCG 34-36 h prior to follicle aspiration were compared to 110 cycles triggered with hCG alone., Results: Serum E2 levels were significantly lower on the day of hCG treatment in the FSH-treated group (266 vs. 297 pg/ml). On the day after hCG administration, serum E2 was similar in both groups. Maximum follicular diameters the day of and the day after hCG treatment were similar as were the number of oocytes aspirated and embryos transferred, and clinical pregnancy rates in both groups. The number of cycles dropped due to premature luteinizing-hormone (LH) surge was 8% in the FSH group compared to 20% in the group treated with hCG alone., Conclusions: A midcycle FSH boost does not increase pregnancy success of unstimulated IVF cycles but does enhance the increase in serum E2 levels after hCG, thereby potentially allowing earlier hCG administration while incurring decreased cycle cancellation rates due to premature LH surges.

A potent gonadotropin-releasing hormone (GnRH) antagonist (Nal-Glu) was administered to downregulate the pituitaries of oocyte donors (n = 15) and block their midcycle luteinizing hormone surges. Donors received Nal-Glu at a dose of 50 microg/kg/day i.m., beginning when lead follicles reached a mean diameter of 14 mm. All donors had previously undergone controlled ovarian hyperstimulation cycles using GnRH agonist (leuprolide acetate) administered subcutaneously beginning during the midluteal phase. Ovarian stimulation was performed using human menopausal gonadotropin (hMG). Compared to previous stimulated cycles using agonist and hMG, cycles with antagonist and hMG demonstrated a significant decrease in the amount of hMG required for follicle stimulation (24.7 +/- 1.8 vs. 31.3 +/- 2.5 ampules; p < 0.05). There was also a significant reduction in the number of patient visits necessary per cycle (5.1 +/- 1.4 vs. 9.3 +/- 1.1; p < 0.05) and the required duration of treatment to accomplish a cycle (27.1 +/- 5.3 vs. 11.3 +/- 1.3 days; p < 0.05). However, there were no differences noted in the number of oocytes retrieved (10.7 +/- 4.5 vs. 13.0 +/- 6.3), the fertilization rate of oocytes (60.3 +/- 10.2 vs. 53.9 +/- 11.6%), or the number of embryos obtained per recipient (5.5 +/- 3.2 vs. 7.6 +/- 5.3). Clinical pregnancies occurred in 7 of 15 transfer cycles to recipients. There were no serious adverse side effects experienced by donors using antagonist. We conclude that the use of GnRH antagonist significantly reduces the amount of medication and the time required for ovarian hyperstimulation and that is a useful adjunct in cycling oocyte donors.

We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation.

Population and insemination studies indicate that women experience declining fertility with ageing. The question therefore arises whether older women are suitable oocyte donors. This study addresses this issue by examining the relationship between oocyte donor age and clinical outcome in a large oocyte donation programme. We retrospectively reviewed data from 458 consecutive oocyte donation cycles completed by 164 different designated oocyte donors. Data were divided into two groups: group A, cycles with donors aged 21-30 years at the time of follicular aspiration (193 cycles, 88 donors); and group B, cycles with donors aged 31-40 years at the time of follicular aspiration (265 cycles, 86 donors). Five donors, because of ageing during repetitive donations, contributed data to groups A and B. In a given cycle, all oocytes for a recipient came from only one designated donor. Comparing the two donor groups, there was no difference in the amount of gonadotrophin used to achieve optimal stimulation; however, more oocytes were obtained from group A than group B donors (16.8 +/- 6.9 and 15.1 +/- 8.1 respectively, P < 0.05). Similar percentages of oocytes were fertilized in each group, resulting in the transfer of comparable numbers of embryos (4.5 +/- 1.1 and 4.4 +/- 1.3 respectively). Comparable clinical pregnancy rates were achieved (group A, 36%; group B, 37%). The spontaneous abortion rates were also similar (group A, 20%; group B, 12%), resulting in comparable ongoing and delivered pregnancy rates per cycle (group A, 29%; group B, 32%) and per embryo transferred (group A, 6.4%; group B, 7.3%). In conclusion, women of proven fertility should not be excluded from donating oocytes simply because of their age. There exists a cohort of fertile women who resist the decreasing fecundity and increasing spontaneous abortion rates associated with ageing. With careful screening, many women of proven fertility can donate oocytes until the age of 40 years with an efficacy equal to that of younger women. Given the relative shortage of suitable oocyte donors, and increasing requests from recipients with previous donor oocyte babies to obtain oocytes from the same, now older, donor, the findings of this study are of practical clinical importance.

Objectives: To define the incidence and severity of ovarian hyperstimulation syndrome (OHSS) occurring in oocyte donors., Methods: Women (n = 149) aged 31.3 +/- 4.8 years (mean +/- S.D., range 21-41 years) participated as designated oocyte donors and underwent 400 consecutive cycles of controlled ovarian stimulation using human menopausal gonadotropin following pituitary downregulation with gonadotropin-releasing agonist. Patients were monitored by serial transvaginal ultrasound examinations and serum estradiol (E2) determinations. Oocytes (15.6 +/- 7.5 per aspiration; range 2-57) were harvested by ultrasound-directed transvaginal follicle aspiration 36 h following the intramuscular injection of human chorionic gonadotropin (hCG). Follow-up examination occurred 1 and 2 weeks post-aspiration., Results: On the day of hCG injection E2 levels ranged from 512 to 13,502 pg/ml (mean 2902.7 +/- 1486.9 pg/ml). Over the next few weeks the degree of hyperstimulation in donors was staged: mild 65% (grade I, n = 98; grade II, n = 162); moderate 33.5% (grade III, n = 120; grade IV, n = 14); severe 1.5% (grade V, n = 6; grade VI, n = 0). Associated preaspiration E2 levels were: grade I, 1120 +/- 424 pg/ml; grade II, 2084 +/- 613 pg/ml; grade III, 3785 +/- 1713 pg/ml; grade IV, 5370 +/- 1264 pg/ml; grade V, 4286 +/- 1100 pg/ml. Worsening OHSS was associated with increasing levels of E2. There were no serious complications and hospitalization was not required. All symptoms resolved within 30 days of aspiration, disappearing by the time of the first menstrual flow in women of grade-III or lower stage., Conclusion: Although oocyte donors commonly experienced exaggerated levels of serum E2 they rarely (< 2%) developed severe OHSS. This may be attributable to their lack of embryo transfer which avoids exacerbating the illness.

Objective: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles., Study Design: We compared cycles with elevated day 3 FSH levels (> 20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels., Patients: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH., Results: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E2) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies., Conclusions: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.

An early marker predictive of a viable pregnancy would ease the anxiety associated with positive pregnancy tests after the use of donor oocytes. We examined the predictive value of an early serum quantitative human chorionic gonadotrophin (Q-HCG) concentration on pregnancy outcome following oocyte donation. Embryo transfers after oocyte donation resulting in a positive serum beta-HCG were examined beginning 9 days after embryo transfer from those samples assayed in our laboratory (n = 77). Q-HCG concentrations were measured in our laboratory by an immunoradiometric assay utilizing the first International Reference Preparation. Implantations were defined as the number of gestational sacs visualized by transvaginal ultrasound 21 days after embryo transfer. Biochemical pregnancies were those with transient elevations in beta-HCG concentration but without implantation sites. Spontaneous abortions were characterized by an implantation site with the eventual arrest of development. Ongoing/delivered pregnancies developed appropriately and proceeded beyond the first trimester. Day 9 Q-HCG concentrations did not differentiate between biochemical pregnancies/spontaneous abortions and ongoing/delivered pregnancies, although mean +/- SD concentrations for biochemical pregnancies were significantly lower than those for the other groups (P < 0.0001): biochemical pregnancies, n = 18, 5.8 +/- 8.9 mIU/ml, range 0-35; spontaneous abortions, n = 2, 46.0 +/- 10.0 mIU/ml, range 39-53; ongoing/delivered pregnancies, n = 57, 41.5 +/- 35.4 mIU/ml, range 0-214. In addition, day 9 Q-HCG concentrations did not differentiate between multiple implantations, although the implantation of four sacs had a significantly higher mean Q-HCG concentration compared with the implantation of fewer sacs (P < 0.0001): one sac, n = 22, 32.2 +/- 21.5 mIU/ml, range 3-78; two sacs, n = 25, 35.8 +/- 21.3, range 0-81; three sacs, n = 7, 47.1 +/- 37.1 mIU/ml, range 22-126; four sacs, n = 4, 122.3 +/- 62.4 mIU/ml, range 76-214. The positive predictive value of a Q-HCG > 10 mIU/ml was 0.91 (sensitivity 91%, specificity 75%). These initial data suggest that early day 9 serum Q-HCG determinations do not accurately identify viable pregnancies or multiple implantations. Even an early negative pregnancy test should be repeated because it can be associated with a normal pregnancy.

Objective: To examine the null hypothesis that women with polycystic ovary syndrome (PCOS) produce similar levels of prorenin and other components of the ovarian-derived prorenin to angiotensin cascade (ODPAC) at baseline and after stimulation with clomiphene citrate (CC) or hMG when compared with normal age- and weight-matched ovulatory controls., Design: Prospective controlled clinical trial., Setting: Infertility clinic in a university-based county hospital and a hospital-based private infertility practice., Patients: Twenty-eight infertile women aged 18 to 35 years. Thirteen patients were diagnosed with PCOS. Fifteen normal ovulatory patients who were matched for age and weight served as controls., Interventions: Twenty patients were stimulated with CC and eight were stimulated with hMG., Main Outcome Measures: Serum E2, P, T, androstenedione (A), DHEAS, LH, FSH, and plasma prorenin, active renin, and angiotensin II (Ang II) were measured at baseline and during the preovulatory and midluteal phases of the stimulation cycles., Results: Baseline plasma prorenin in PCOS was higher than that of follicular phase controls. Plasma prorenin correlated significantly with peripheral androgen levels. Prorenin, active renin, and Ang II increased in response to gonadotropins with the largest increases occurring in control patients receiving CC. An association was seen between ovulation with CC and lower baseline levels of active renin., Conclusions: The null hypothesis was rejected. Infertile women with PCOS have higher baseline prorenin levels when compared with age- and weight-matched ovulatory controls. There is a significant correlation between prorenin and the peripheral levels of androgens produced during ovarian stimulation. Baseline active renin levels may be predictive of ovulation with CC.

Objective: To describe the reproductive and obstetric outcomes of women > or = 50 years attempting pregnancy using donor oocytes., Setting: The IVF program at the University of Southern California., Patients: Thirty-six postmenopausal women aged 50 to 59 years, mean 52.3 +/- 2.6 years (mean +/- SD) were screened medically, reproductively, and psychologically and enrolled in a trial of oocyte donation., Interventions: Recipients underwent hormone replacement therapy using oral micronized E2 and IM administered P. Oocytes were provided by designated gamete donors (mean age 30.5 +/- 4.4 years). Embryos (4.3 +/- 1.2) were transferred transcervically., Main Outcome Measures: Rates for embryo implantation, spontaneous abortion, ongoing and delivered pregnancies, as well as the gestational age at delivery, birthweights, complications, and postpartum outcomes., Results: Forty-five aspirations resulted in 22 pregnancies (48.9%): 3 preclinical, 2 ending in spontaneous abortion, and 17 viable pregnancies (37.8%). The embryo implantation rate was 20.6%. Nine of 17 pregnancies (52.9%) were multiple gestations (6 twins; 1 triplet; and 2 quadruplets, selectively terminated to twins). All pregnancies delivered beyond 32 weeks: mean gestational age for singletons was 38.4 +/- 1.9 weeks (range 35 to 41 weeks); mean gestational age for twins was 36.3 +/- 1.4 weeks (range 34 to 38 weeks); the triplet pregnancy delivered at 32 weeks. Complications occurred in eight patients; gestational hypertension (n = 7), preterm labor (n = 3), gestational diabetes (n = 2), and pre-eclampsia (n = 1). One infant was trisomy-21., Conclusion: Patients > or = 50 years experience similar pregnancy rates after oocyte donation as younger women and are at equal risk for multiple gestation. Antenatal complications were experienced by the majority of patients, underscoring the importance of high risk obstetric surveillance and care.

The experience of transferring embryos produced through in-vitro fertilization (IVF) utilizing donated oocytes and spermatozoa is described. Recipients (n = 28; aged 38-59 years) received oral micronized oestradiol and i.m. progesterone and were synchronized to donors undergoing ovarian stimulation. Reasons for selecting therapy included advanced reproductive age (> 42 years; n = 21) or hypergonadotrophic hypogonadism (n = 7), combined with severe male factor infertility in 23 couples. Five women were single and without partners. Oocytes were fertilized by cryopreserved spermatozoa designated for use by the recipient. Up to five embryos were transferred transcervically. Supernumerary embryos were cryopreserved. A total of 36 aspirations produced 15.6 +/- 7.3 oocytes per retrieval. In 10/36 cycles (27.8%), embryos were available for cryopreservation. Using fresh embryos, the overall pregnancy rate was 38.9% (14/36), clinical pregnancy rate 33.3% (12/36), and ongoing/delivered pregnancy rate 30.6% (11/36). Three ongoing pregnancies were later established by transferring cryopreserved embryos. Adjusting for these events, the per aspiration overall pregnancy rate per retrieval was 47.2%, clinical pregnancy rate 41.7%, and ongoing/delivered pregnancy rate 38.9%. Implantation rates per individual embryo transferred were 16.6% following fresh embryo transfer. A viable pregnancy was achieved by 14 of 28 women (50% cumulative pregnancy rate). We conclude that using donor oocytes and donor spermatozoa is efficacious and allows couples of whom both members suffer from severe gamete abnormalities and single functionally agonadal women an effective means of achieving pregnancy.

The purpose of this experiment was to determine whether use of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, would prevent the occurrence of ovarian hyperstimulation syndrome (OHSS) in the rabbit model. A total of 20 adult female New Zealand white rabbits were studied. All rabbits received 75 IU of human menopausal gonadotrophin s.c. each day for 7 days. On day 8, all rabbits received 2500 IU of human chorionic gonadotrophin (HCG). Ten rabbits were randomly chosen to receive enalapril orally. Five received 1 mg/kg of enalapril and five received 2 mg/kg of enalapril twice daily. The remainder received placebo orally twice daily. On day 10, all rabbits underwent surgical exploration. Total body weight was found to increase significantly in the placebo group (by 293 g, P < 0.001) but not in either group receiving enalapril. Haematocrit also increased significantly in the placebo group (by 3%, P < 0.013) but not in the enalapril groups. Ovarian weights were highest for the 2 mg/kg enalapril group (5.80 +/- 0.52 g), followed by the 1 mg/kg enalapril group (3.64 +/- 0.45), and least for the placebo group (2.69 +/- 0.17). All 10 placebo rabbits met criteria for severe OHSS whereas only six in the enalapril groups did. We concluded that angiotensin II may play a significant role in the development of weight gain, third space fluid accumulation and intravascular fluid depletion in OHSS. ACE inhibition resulted in a 40% decrease in the incidence of OHSS in the rabbit model.

Oocyte and embryo donation has become increasingly common over the past 10 years. Today, it is successfully used to treat women with a variety of disorders, including ovarian failure, avoidance of genetic disease transmission, declining ovarian function, poor oocyte quality following conventional assisted reproduction, and age-related infertility. Success rates do not appear to vary with the recipient's age or diagnosis, with live birth rates in the 25-35% range. Oocyte and embryo donation represent the most efficacious method of assisted reproduction.

Purpose: Our purpose was to determine whether angiotensin converting enzyme (ACE) inhibitors affect gonadotropin-stimulated estradiol (E2) production., Design: This was a prospective, masked, randomized, placebo-controlled animal trial. Twenty female New Zealand White rabbits were hyperstimulated with gonadotropins. One-half of the rabbits received concomitant treatment with the ACE inhibitor, enalapril; one-half received concomitant treatment with a placebo., Results: Baseline peripheral E2 (13 +/- 4 vs 11 +/- 2 pg/ml) and angiotensin II (Ang II) (22 +/- 5 vs 27 +/- 7 pg/ml) levels were similar in both groups. Significant inhibition of peripheral Ang II levels was achieved in the enalapril group (32 +/- 6 vs 93 +/- 15 pg/ml; P = 0.005). E2 was significantly higher in the rabbits receiving enalapril versus placebo (369 +/- 58 vs 183 +/- 35 pg/ml, P < 0.03), respectively. By day 10, peripheral E2 had returned to normal levels in both groups (13 +/- 1 vs 13 +/- 1 pg/ml). However, E2 levels in the ovarian effluent were 2.8 times higher in the enalapril rabbits., Conclusion: Peripheral Ang II levels increase after gonadotropin stimulation and ACE inhibitors are able to blunt this increase significantly. ACE inhibition has a significant stimulatory effect on ovarian E2 production. This implies that Ang II may normally inhibit ovarian E2 production in stimulated cycles.

Objective: To determine whether angiotensin-converting enzyme (ACE) inhibition would affect ovarian steroid synthesis in the oocyte donors undergoing controlled ovarian hyperstimulation (COH)., Setting: The IVF program of the University of Southern California., Design: Prospective matched clinical trial., Patients: Twelve oocyte donors were studied in 28 hyperstimulation cycles., Interventions: Donors underwent a standard COH protocol. Follicle aspiration was performed 34 hours after administration of hCG. After the procedure, seven donors were administered the ACE inhibitor, captopril, 6.25 mg orally twice daily for 4 days. The remaining patients served as controls., Main Outcome Measures: Serum E2, P, plasma prorenin, active renin, and angiotensin II (Ang II)., Results: Angiotensin II increased after aspiration in both groups but was significantly lower in those receiving captopril. Peak P in the captopril group was significantly lower than controls (81.8 +/- 27.8 versus 208.5 +/- 23.9 ng/mL [conversion factor to SI unit, 3.180]). Peak E2 was significantly higher (2,222.4 +/- 875.3 versus 425.6 +/- 490.4 pg/mL [conversion factor to SI unit, 3.671]). Active renin and Ang II correlated with P., Conclusions: In stimulated cycles, inhibition of Ang II production appears to raise serum E2 and lower P levels. Angiotensin II, therefore, may have a role in the regulation of ovarian steroid synthesis.