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Objective To evaluate the effect of low-dose GH-releasing factor (GRF) on folliculogenesis in regularly menstruating women. Design Prospective clinical trial where individual patients served as their own control. Setting Outpatient Reproductive Endocrine/Infertility Clinic of the Los Angeles County-University of Southern California Medical Center, Los Angeles, California. Patients Seven regularly menstruating women. Intervention During treatment cycles, subjects received 100 μ g SC GRF on cycle days 2 to 11 and were observed during a control cycle. Main Outcome Measures Follicle number and diameter, as well as endometrial thickness were all assessed by vaginal ultrasound and blood was obtained for serum FSH, LH, E 2 , P, GH, insulinlike growth factor 1 (IGF-1), and insulin-like growth factor binding protein-3. Results During cycles treated with GRF, GH, and IGF-1 levels were normal. However, follicular growth rates and E 2 to FSH ratios were significantly higher. The day of the peak E 2 to follicular diameter ratio after GRF was earlier than in control cycles. Endometrial growth rates were also greater with GRF. Conclusions Our data, although preliminary, support the hypothesis that low doses of GRF may independently stimulate the ovary and enhance folliculogenesis.

Clinical impressions suggest the presence of considerable anxiety and depression in infertile couples. We utilized a psychological stress test to assess adaptations to provoked stress to improve the psychological profile of infertile women. A psychological stress test was administered to four groups: normal menstruating females (controls, n=13); oocyte donors (n=13); recipients of oocyte donation (n=7); and women undergoing standard in-vitro fertilization (IVF; mean age 38.0 years; n=8). The psychological stress test consisted of three active coping tasks: (i) serial subtraction, (ii) Stroop colour test, (iii) speech task and (iv) one passive coping task, the cold-pressor test. Haemodynamic responses (HD) were monitored before, during and after the psychological stress test, and serum samples were drawn for catecholamines and cortisol. Baseline blood pressures were similar among groups. The psychological stress test elicited different biophysical responses in controls compared with the other groups (P

Objective: To compare diabetes-associated peptide hormones (DAPHs) and inflammatory markers in the follicular fluid (FF) and serum among polycystic ovary syndrome (PCOS) patients as compared to controls undergoing in vitro fertilization (IVF). Study Design: Levels of DAPHs and inflammatory markers in FF and serum were measured and correlated to IVF cycle outcomes and clinical pregnancy rate in three IVF groups: obese PCOS (n = 8), lean PCOS (n = 12), and controls (n = 11). Methods: Follicular fluid and serum were prosectively collected from obese and lean pcos and control females undergoing IVF. BioFlex ® array was used to analyze all samples from subjects. IVF cycle outcomes were collected on all subjects. Results: Ten DAPHs were assessed. Obese PCOS had higher levels of C-peptide (194.4 ± 163.5 pg/mL, P< 0.03), insulin (172.6 ± 113.6 pg/mL, P< 0.01), and leptin (10,046.1 ± 4920.2 pg/mL, P< 0.05) in FF as compared to lean PCOS and controls. Obese PCOS patients had higher levels of serum leptin (5575.5 ± 1650.2 pg/mL), with a difference in leptin concentrations noted between obese PCOS and controls (P < 0.01) and between obese and lean PCOS patients (P < 0.01). Higher levels of C-peptide (P < 0.04) and leptin (P < 0.01) in the FF were associated with increased total gonadotropin drug usage. There was a trend toward fewer oocytes retrieved (P < 0.06) and significantly lower number of normally fertilized zygotes (P < 0.04), with higher C-peptide levels. A trend toward increased clinical pregnancy rates was noted with lower serum levels of leptin (P < 0.08). Conclusions: DAPHs may play a role in the suboptimal ovarian response seen in obese IVF patients with PCOS as compared to lean PCOS patients and controls. Further studies are needed to understand if the evaluations in DAPH are secondary to obesity itself or are specific to this subset of PCOS patients.

Objective: The objective of this study was to assess the impact of discordant ovarian antral follicle counts (AFCs) on cycle stimulation and live birth in autologous in vitro fertilization (IVF) cycles. Materials and Methods: This is a retrospective analysis of first-time cycles of 153 patients undergoing gonadotropin-releasing hormone-antagonist IVF. Results: While AFC significantly correlated with cycle stimulation characteristics, only the right ovarian AFC significantly correlated with live birth (r = 0.18, P< 0.02). Right ovarian AFC was significantly greater in live birth cycles (12.3 ± 7.8) compared to cycles without a live birth (9.6 ± 6.0, P< 0.02). Using ≤ 7 as a threshold of low unilateral AFC, concordant low AFC was present in 28% (Group 1: n = 43); discordant low left and normal right in 13% (Group 2: n = 19); discordant low right and normal left in 11% (Group 3: n = 17); and concordant normal in both ovaries in 48% (Group 4: n = 74) of patients. Live birth was similar in Group 2 (36.8%), Group 3 (35.3%), and Group 4 (37.8%), but significantly less in Group 1 (9.3%) (P < 0.05). Conclusion: Live birth was higher with greater right AFC. Using threshold AFC, adverse outcomes were only noted when both ovaries had low counts. Individual AFC may serve as a more specific indicator than total AFC as a marker of ovarian reserve.

The past decade has seen increased success rates with assisted reproductive technologies (ART), however, the overall pregnancy and implantation rates have remained relatively low. These low rates continue even though we now have improved stimulation protocols and laboratory techniques. Three areas that have gained specific attention include 1) identification of the optimal uterine environment; 2) extended embryo culture to the blastocyst stage; and 3) the embryo transfer (ET) technique, which has historically been viewed as an unimportant variable in the success of an ART treatment cycle..

We assessed insulin sensitivity in women comparing the insulin tolerance test (ITT) with the intravenous glucose tolerance test with frequent sampling and computer modeling (FSIVGTT) and evaluated the effects of hormonal therapy in postmenopausal women using both methods.This prospective study tested 18 premenopausal women and ten postmenopausal women randomized to receive either estrogen alone or estrogen with a sequential progestin for 6 months at a menopause research clinic. All subjects received an ITT and an FSIVGTT within 48-72 hours of each other in random sequence. Postmenopausal women were then randomized to receive either 0.625 mg conjugated equine estrogen for 6 months or 0.625 mg conjugated equine estrogen with medroxyprogesterone acetate, 10 mg, for 10 days each month for 6 months. Both the ITT and the FSIVGTT were repeated following hormonal therapy at 2 and 6 months. Plasma insulin and glucose were measured; insulin sensitivity was calculated after the ITT (Kitt) and the FSIVGTT (Si) at each visit in each group.A close correlation was found between Kitt and Si values at initial testing in both pre- and postmenopausal women and following both types of hormonal therapy (r = 0.76 for all tests, P.001). A reduction in insulin sensitivity was observed in postmenopausal compared to premenopausal women; this occurred in five of ten postmenopausal women using the Kitt measurement and in four of ten women using Si. Estrogen replacement had a beneficial effect on insulin sensitivity. While Kitt increased by 24.2 +/- 9.6% (P.05), the increase in Si (6.7 +/- 18%) was not significant because of the variability with this measurement. An attenuation in insulin sensitivity was seen with added progestin. Kitt values decreased by 17.7 +/- 7.7% and Si values by 31.9 +/- 12%. Similar findings were noted at 2 and 6 months.The ITT and FSIVGTT provide quantitatively similar information regarding insulin sensitivity in healthy women. A mild degree of insulin resistance appears to be present in some healthy postmenopausal women. Estrogen appears to improve insulin sensitivity, while added progestin may attenuate this beneficial effect.

OBJECTIVE We assessed the effects of progestin when added to estrogen on the adaptive patterns to provoked stress in postmenopausal women. METHODS Fourteen postmenopausal women were randomized to receive either a transdermal estrogen patch (TE2) (n = 7) for 6 weeks or TE2 with added medroxyprogesterone acetate (10 mg) (TE2/MPA) (n = 7) for the last 10 days of the 6-week regimen. Behavioral stress tests were administered to each group, with measurements of biophysical and neuroendocrine responses. In a crossover fashion, after each group received the first treatment and testing, treatment was continued for another 6 weeks with the alternate regimen, at which time another stress test was administered. Responses to stress in the two treatment groups were compared to each other and to established placebo responses. RESULTS Biophysical responses in the TE2 group were significantly blunted compared to both TE2/MPA and placebo responses (P < .05). Without MPA treatment, there were significantly blunted speech (P < .05) and cold pressor (P < .01) blood pressure responses. With added progestin, there was a greater systolic blood pressure response (P < .01) compared with estrogen alone. Both groups (TE2 and TE2/MPA) had blunted and nonsignificant responses of ACTH and cortisol upon testing, whereas the placebo group showed a significant response (P < .01). Plasma norepinephrine responses, however, were significantly blunted after TE2, compared with the increased responses observed with both TE2/MPA and placebo (P < .01). CONCLUSION Although estrogen significantly reduces behaviorally induced stress reactivity in postmenopausal women, certain doses of progestin administration may blunt this effect.

Issues surrounding egg donation informed consent have recently been spotlighted due to advances in medical genetics. We sought information on attitudes and desires of donors and recipients to craft a program policy on counseling, disclosures, and re-contacting participants.Between April 2003 and September 2006 we conducted a questionnaire-based evaluation in our oocyte donor program. Donors pre-donation (n=265) and those undergoing the process (n=60), and recipients either ante- or postpartum (n=57), were asked about their desire to know/disclose obstetric outcomes (Question 1); willingness for contact in the event of a medical emergency (Question 2); and wish to know/disclose a liveborn's medical condition (Question 3).Pre-donation questioning among all donors generally revealed reticence to Question 1 (31% [n=83]), but were overall amenable with Questions 2 and 3 (83% [n=220] and 83% [n=219]). Following the donation process, no differences in Questions 1 and 2 were noted, but fewer donors were amenable with Question 3 (pre-donation 93% [n=56] versus post-donation 38% [n=23]; P0.01). Overall, recipients were amenable to all three questions (88% [n=50], 74% [n=42] and 88% [n=50]), with similar responses both ante- and postpartum.All programs participating in gamete donation should establish a comprehensive disclosure policy, including consents that are built upon effective lines of communication between clinical staff and legal counsel assuring that parentage, relinquishment, and re-contact information in donor-recipient agreements are consistent with clinic consent documents and desires of both parties; All decisions must be adequately documented and honored and long-term counseling needs should be addressed.

We evaluated the rate of blastocyst development in day 3 embryos with appropriate cellular division and investigated whether maternal age modified the effect of embryo fragmentation on blastulation. Our data showed a significant negative correlation between the degree of embryo fragmentation and rate of blastocyst development, but age did not exert an effect on the degree of fragmentation in embryos with appropriate cleaving status, nor did it modify the significant effect embryo fragmentation had on blastocyst formation.

OBJECTIVE: Our purpose was to determine the pattern of reactivity to stress in premenopausal and postmenopausal women and to assess the effects of estrogen. STUDY DESIGN: A behavioral stress test was given to premenopausal ( n = 13) and postmenopausal women ( n = 36). Biophysical and neuroendocrine responses were measured during and on completion of the stress test. The postmenopausal women were then randomized to placebo or transdermal estradiol treatment for 6 weeks, at which time another behavioral stress test was given. RESULTS: Stress reactivity to math and speech tasks elicited significantly greater systolic blood pressure responses in postmenopausal women compared with premenopausal women ( p \lt 0.05). On retesting, significant biophysical responses that were present during the initial stress testing were still present ( p \lt 0.05) in the placebo group but were blunted with estrogen treatment. Plasma corticotropin, cortisol, androstenedione, and norepinephrine increased during testing to a similar degree in premenopausal and postmenopausal women; this response was maintained after placebo treatment. Postmenopausal women treated with estrogen had blunted responses. CONCLUSION: Significant differences in responses to psychologic stress exist in premenopausal and postmenopausal women. The lack of adaptation may account in part for the increased risk of cardiovascular disease in postmenopausal women. Estrogen appears to blunt the stress-induced response. (AM J OBSTET GYNECOL 1992;167:1831-6.)

To study the effect of endometrial thickness (ET) and echogenic pattern (EP) in oocyte donation cycles upon pregnancy outcomes.Seventy-nine cycles resulting in blastocyst embryo transfer were evaluated. Donors underwent ovarian hyperstimulation using rFSH and GnRH-antagonist. Recipients were synchronized to donors using GnRH-agonist down-regulation followed by fixed dose of estrogen (E2) and progesterone (P4) following hCG. Transvaginal ultrasound (US) obtained ET and EP 10-11 days after initiation of E2 and on day of embryo transfer. Primary outcome was ET and EP in pregnant and non-pregnant cycles. Stimulation and embryology data was analyzed in donors to assess differences prior to transfer.Fifty-nine cycles resulted in clinical pregnancy. No differences were observed in pregnant vs. non-pregnant cycles in proliferative or secretory ET and EP. Similar baseline and stimulation characteristics were found in pregnant and non-pregnant cycles. Regression analysis showed end thickness were not predictive of pregnancy outcomes.Endometrial characteristics in recipients prior to and following progesterone were not predictive of pregnancy outcomes.

To compare the flareup GnRH-antagonist (GnRH-ant) and GnRH-agonist (GnRH-a) protocols in oocyte donation cycles, using the donor as her own control.A retrospective review at a university-based practice of 22 oocyte donors who underwent 29 cycles using recombinant follicle-stimulating hormone (FSH) and GnRH-ant and 28 cycles using flareup GnRH-a with recombinant FSH. Recipients (n=57) were synchronized with estrogen and progesterone supplementation.The total number of recombinant FSH used and days of stimulation were similar between the groups; however, cycle days 5 estradiol (341 +/- 40 vs. 473 +/- 62 pg/mL), peak serum estradiol (1721 +/- 170 vs. 3625 +/- 295 pg/mL) and the number of retrieved MII oocytes (17 +/- 1.5 vs. 29 +/- 7) were significantly higher in the flareup GnRH-a group. Similar fertilization rates, embryos transferred, clinical pregnancy rate/embryo transfer (44%, 11/25; vs. 55%, 15/27), delivered pregnancy rate/embryo transfer (32%, 8/25; vs. 52%, 14/27) and implantation rates (31 +/- 6% vs. 28 +/- 5%) were seen in each group.Both the flareup GnRH-a and GnRH-ant are shortened, simplified and efficacious protocols in oocyte donation cycles.

Objective To identify cervical stenosis and review medical, surgical, and radiological modalities to access the uterine cavity. Materials and methods Computerized searches of Medline and PubMed from 1996 to 2005 were conducted using the key words "cervix," "cervical ripening," and "cervical stenosis." References from identified publications were manually searched and cross-referenced to identify additional relevant articles. We review relevant techniques on how to access the uterine cavity when cervical stenosis is encountered. Results Many gynecologic procedures require uncomplicated access through the cervix to access the uterine cavity, including hysteroscopy, dilation and curettage, sonohysterogram, hysterosalpingogram, endometrial biopsy, and embryo transfer for in vitro fertilization. These procedures can be quite complicated when a cervix is obstructed. Management techniques described include the medical use of misoprostol and laminaria, intraoperative ultrasound guidance, and operative creation of a new passage. Additionally, techniques for bypassing the obstructed cervix and preventing cervical stenosis have been described. Conclusions Cervical stenosis can result in iatrogenic complications. Preoperative identification, cervical ripening agents, osmotic dilators, and the use of ultrasound guidance are useful in overcoming cervical stenosis. It is also key to identify those at risk for cervical stenosis and implement preventative techniques as needed.

Objective The purpose of this study was to evaluate sonohysterography in patients with endometrial cancer and to determine whether (1) transtubal fluid spill occurs during routine sonohysterography, (2) a critical infusion volume for spill exists, or (3) disseminated cancer cells demonstrate viability. Study design At laparotomy, sonohysterography was performed on 16 patients with endometrial adenocarcinoma. Volumes at which tubal spill occurred were recorded. Collected specimens were processed and incubated. After evaluation for viable cells, cytologic analysis was undertaken. Results The median volume that was required for adequate sonohysterography was 8.5 mL. Five patients (31%) had transtubal spill. With an additional saline solution flush, the median total volume for a spill was 20.5 mL. Two patients (12.5%) had viable benign cells that were cultured after routine sonohysterography. One patient (6%) had nonviable carcinoma cells that were identified. Conclusion Transtubal spill occurs during sonohysterography. No critical spill volume was identified. A highly diagnostic tool when abnormal bleeding is evaluated, sonohysterography has a low probability of cancer cell dissemination.

To assess the impact of serum estradiol upon oocyte donor cycle stimulation characteristics and clinical outcomes using flexible GnRH-antagonist (GnRH-ant) with additional FSH supplementation.A retrospective chart review of 99 oocyte donor cycles using ovarian hyperstimulation with recombinant FSH (rFSH) and GnRH-ant was analyzed. Following discontinuation of oral contraceptives, controlled ovarian hyperstimulation was begun using rFSH (150-300 IU daily). GnRH-ant (ganirelix, Organon) and an additional 75 IU of FSH/day were begun when lead follicles were 13-14 mm in greatest diameter. Cycles were analyzed based on serum estradiol response following administration of GnRH-ant (Group 1: progressive rise and Group 2: no rise or a decline). Primary endpoints were cycle stimulation characteristics based on serum estradiol following GnRH-ant, clinical pregnancy and implantation rates.A decline in serum estradiol was seen after GnRH-ant administration in 45% of cycles. Clinical pregnancy rates per transfer (70 vs. 72%) and implantation rates (43 vs. 56%) were similar for each group.Flexible regimens of GnRH-ant even with additional rFSH in a 'step-up' fashion frequently result in a decline in serum estradiol during ovulation induction. While our study is non-randomized, it does not appear to result in any adverse affect in clinical outcomes in donor oocyte cycles.

Use of recombinant follicle stimulating hormone (rFSH) in a cartridge pen device offers obvious benefits for donor oocyte cycles including the administration of fewer and more patient-friendly injectable medications.In a University-based IVF program, a total of 98 oocyte donor cycles using rFSH either reconstituted or as a pen device given to 118 recipients (eight split cycles) were retrospectively reviewed. Following discontinuation of oral contraceptive, controlled ovarian hyperstimulation was begun using either reconstituted rFSH (n = 19) or rFSH with a cartridge pen device (n = 79) (150-300 IU qd). GnRH-antagonists (Ganirelix, Organon) and an additional 75 IU of rFSH/day were begun when lead follicles were 13-14 mm in greatest diameter. The primary endpoints analyzed included cycle stimulation characteristics for each donor group and donor medication tolerance assessment with respect to each rFSH formulation, while secondary outcome measures included clinical pregnancy and implantation rates.Oocyte donors using the pen required significantly less rFSH (2734 IU vs. 3276 IU, p0.05) and scored significantly higher medication tolerance scores (3.9 +/- 0.4 vs. 3.1 +/- 0.6, p0.05). No other differences in cycle stimulation for oocyte donors and clinical outcomes for recipients were seen including pregnancy rates (pen, 77% vs. reconstituted, 55%, p - NS) and clinical pregnancy rates (61% vs. 45%, p - NS). However, significantly greater implantation rates (57% vs. 31%, p0.01) occurred in the pen group.Compared to reconstituted formulations, the pen device results in lower gonadotropin requirements and provides a simplified dosing method with better tolerance.

Chronic pelvic pain can result from noncommunicating uterine cavities in patients with müllerian anomalies. Traditional management has been to resect the noncommunicating uterine horn. Two cases are described. One had a unicornuate uterus with noncommunicating left uterine horn (American Fertility Society [AFS] classification IIb) and the other had a normal external uterine contour with noncommunicating left uterine cavity that did not fit any category of the AFS classification of müllerian anomalies. Attempts at connecting the noncommunicating cavities hysteroscopically failed in both cases. Successful unification of the cavities was subsequently achieved in the first case using the classic Strassman metroplasty with the assistance of the robot. The unification of uterine cavities was achieved using a modified Strassman metroplasty in the second patient, as there was no uterine horn for landmark. Robot assistance was utilized in this case as well. Both patients are symptom free after surgery. We conclude that laparoscopic Strassman metroplasty, with or without robot assistance, is a viable alternative to resection of uterine horns in patients with hematometra, chronic pelvic pain, and noncommunicating uterine cavities.

Objective To assess information needs and decision making among couples donating embryos for stem cell research from outside programs. Design Qualitative and quantitative interview report. Setting Academic medical center. Patient(s) Forty-five couples donating embryos to stem cell research. Main Outcome Measure(s) Likert scales were used to assess whether participants regarded embryos as children and whether donation was analogous to organ or blood donation. Use of counseling, consideration of disposition options, and value of the interview were assessed. Recorded responses were analyzed for themes. Result(s) The average length of cryopreservation was 4.8 years. Twenty percent of the embryos were created with donor gametes; 53% of respondents viewed embryos as completely different from children; 31% and 27% considered embryo donation "identical" to organ and blood donation, respectively; 47% chose stem cell research to help others; 96% had not sought counseling in making their decision; and 20% were told they could not donate embryos to other couples. Conclusion(s) Although many couples had questions/concerns regarding disposition, few sought formal counseling. Outside programs may unnecessarily limit the option of donation to other couples. Guidelines are needed to ensure that couples making embryo disposition decisions are properly informed of all options, that third-party gamete issues are addressed, and that psychological support is offered.

Uterine fibroids are a major gynecologic problem in American women, and several alternatives have been developed. Conservative treatment, with the goal of treating the fibroid but retaining the uterus, is a frequent choice among women who require therapy during their early to middle reproductive years. A variety of conservative surgical approaches exist; each has advantages and disadvantages for the clinician and the patient. Some are well-established techniques, whereas others are still in the investigational stage. None has been evaluated adequately for its effects on future fertility. To this end, it is imperative that investigators continue to evaluate these surgical procedures so that the clinician can provide accurate and comprehensive information when faced with a patient who desires one or more of these approaches. Furthermore, it is critical for the practitioner to stay informed about these procedures so that patients can be given a full complement of options.

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.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.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.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.

This review is designed to discuss the literature, published from December 2002 to January 2004, on the non-surgical treatment of fibroid. All established and new modalities are reviewed, and all new developments in the field are discussed. The resulting impact on the treatment of infertility will also be evaluated.In the past year important advances occurred in the medical treatment of uterine fibroids. It was found, in a large randomized trial, that preoperative treatment with gonadotropin-releasing hormone analogue did not improve surgical results or decrease blood loss. However, important strides were made in understanding the molecular biology of the effect of the hormone analogue on fibroids. Other medical therapies investigated include danazol, raloxifene, mifepristone, aromatase inhibitors, and the levonorgestrel-containing intrauterine device. Most promising in terms of long-term usage for reduction of size and symptoms appears to be the combination of gonadotropin-releasing hormone analogue and raloxifene, although selective progesterone receptor modulators may also achieve this aim. However, none avoid producing an anovulatory state that inhibits fertility, and none have been shown to enhance fertility following discontinuation. Uterine artery embolization is another non-surgical technique under intense investigation. The year's literature suggests that while results are comparable with hysterectomy in terms of complication rate and patient satisfaction, there may be important issues for women who wish to undergo the procedure and retain future fertility. Specifically, there is a significant rate of premature ovarian failure, as well as occasional damage to the endometrial vasculature with resulting atrophy and adhesion formation. Improvements in technique, in particular the use of larger and more spherical microspheres for embolization, may reduce these unwanted effects. However, few data exist regarding the course of pregnancy and outcome following embolization.A number of non-surgical treatments exist for uterine fibroids, but none has been shown to be of value in the patient desiring future fertility. Myomectomy remains the standard of care for such women, and all other therapies should be designated experimental and limited to appropriate investigational studies.

The medical treatment of endometriosis has long centered upon producing a hypoestrogenic environment by producing pituitary suppression or a progestin-dominant environment. However, as more is uncovered regarding the pathogenesis and pathophysiology of this disease, more targeted therapies can be developed. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. These include progesterone receptor modulators, gonadotropin releasing hormone (GnRH) antagonists, aromatase inhibitors, tumor necrosis factor alpha (TNF-α) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, pentoxifylline (and other general immune modulators), and estrogen receptor beta agonists. It is hoped that this new wave of medications will improve the response to medical therapy for this disorder.

Endometriosis and infertility have been linked in the discipline of gynecology for more than a century. There is evidence that endometriosis can and does decrease fertility. However, our ability to determine fertility prognosis based on a staging system is severely limited. Treatment options include medical therapy, surgical intervention, and assisted reproduction. For endometriosis-associated infertility, medical therapy seems to have no value alone. Surgical therapy is beneficial for all stages of diseases, as in assisted reproduction. The relative value of these two latter approaches, however, is untested. Our suggestions for the treatment of early-stage endometriosis are surgery and/or superovulation with intrauterine insemination as first-line treatments. For more advanced disease, with tubal damage, surgery or in vitro fertilization are options. For the most advanced cases, in vitro fertilization preceded by 3 months of medical treatment of the endometriosis is advised.

Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the same size as later pregnancy hCG as judged by SDS gel electrophoresis. A series of Western blot analyses and immunoassays conducted with the samples either non-reduced or reduced showed that B152 is directed to a linear epitope located in the COOH-terminal peptide region of the beta subunit. This indicated that only the O-glycan groups and not the N-linked glycans are part of the antibody epitope.

This study was conducted to assess the outcomes of TESA in women undergoing oocyte donation. Descriptive reports from a university IVF practice were reviewed to evaluate the outcomes of women (n = 10) who underwent 12 cycles of ovum donation and required testicular sperm aspiration due to obstructive azoospermia (n = 6) and nonobstructive azoospermia (n = 4). Percutaneous needle aspiration of the testes was performed prior to oocyte retrieval to recover sperm, and intracytoplasmic sperm injection was subsequently performed on the donated oocytes. Fertilization was documented 16-18 h later and transcervical embryo transfer performed 72 h postretrieval. Successful retrieval of testicular spermatozoa utilizing the percutaneous technique was achieved in all 12 cycles. All cycles resulted in an ET with the achievement of 7 (58%) pregnancies, of which 5 (42%) are ongoing or delivered. The individual embryo implantation rate was 18.4% (9/49). Two cycles (16.6%) produced supernumerary embryos for cryopreservation. TESA represents a simple procurement technique associated with minimal morbidity. It may be offered even in cases of nondestructive azoospermia.

Women with polycystic ovary syndrome (PCOS) have chronic anovulation and hyperandrogenism and frequently have abnormalities in their lipid profiles and insulin/insulin-like growth factor axis that increase their lifetime risk for cardiovascular disease. Normal ovulatory women may have polycystic ovaries on ultrasonography and yet lack the clinical features of PCOS. To further explore whether ovulatory women without clinical/biochemical hyperandrogenism but with polycystic appearing ovaries (ov-PAO) have subclinical features of PCOS, we prospectively characterized 26 ov-PAO women and matched them by age and body mass index to 25 ovulatory women with normal appearing ovaries (ov-NAO) and to 22 women with PCOS. After an overnight fast, all women had baseline endocrine and metabolic assessments. In addition, a subset of each group of women underwent GnRH-agonist (leuprolide acetate 1 mg sc) testing, ACTH stimulation, and an insulin tolerance test (ITT). At baseline, ov-PAO and ov-NAO women had similar endocrine profiles (LH, LH:FSH, androstenedione, and DHEAS). Compared with ov-NAO, 31% of ov-PAO women had reduced glucose responses after insulin (Kitt), suggesting mild insulin resistance, and 35% had high density lipoprotein levels below 35 mg/dL, a level considered to represent significant cardiovascular risk. After GnRH-agonist, ov-PAO women had response patterns in LH, total testosterone, and 17-hydroxyprogesterone (17-OHP) that were intermediate between ov-NAO and women with PCOS. Ovarian responses were above the normal range in 30–40% of women with ov-PAO. In ov-PAO, peak responses of LH after leuprolide correlated with triglyceride levels (P < 0.05) and peak responses of 17-OHP correlated inversely with Kitt values (P < 0.05). No significant differences were noted with ACTH testing. In conclusion, occult biochemical ovarian hyperandrogenism may be uncovered using GnRH-agonist in ovulatory women with ov-PAO, while adrenal responses remain normal. Subtle metabolic abnormalities may also be prevalent.

Objective: To report a case of cryptic 21-hydroxylase deficiency identified at the time of ovum donation in a patient with Turner's syndrome. Design: Case report. Setting: University IVF practice. Patient(s): A 28-year-old woman with Turner's syndrome who presented for ovum donation. Intervention(s): Four cycles of donor IVF. Main Outcome Measure(s): Pregnancy, endometrial appearance, progesterone, and 17-hydroxyprogesterone values. Result(s): The patient failed two fresh and two frozen ET cycles with donated oocytes. The appearance of the endometrium suggested elevated progesterone before progesterone supplementation. An elevated progesterone was detected but not suppressed by leuprolide acetate. Progesterone was suppressed by adding dexamethasone. The diagnosis of cryptic 21-hydroxylase deficiency was confirmed biochemically. Conclusion(s): Patients with Turner's syndrome reportedly have poorer outcomes with donor IVF than other women. They also have an increased incidence of carrying a defective 21-hydroxylase gene. We suggest that some of the poorer outcomes may be explained by the presence of elevated progesterone and recommend evaluation of possible congenital adrenal hyperplasia in patients with Turner's syndrome who want oocyte donation.

Objective: To describe the establishment of an embryo donation program using a large oocyte donor registry to produce embryos. Design: Descriptive study. Setting: A university-based practice. Patient(s): Embryos were obtained either through traditional donation from couples who underwent IVF-ET (n = 8) or through ovum donation (n = 15) with embryos produced by the program. In select cases, ovum donors were inseminated either with donor sperm selected following an advance directive from the patient or couple (n = 13) or with sperm designated by an IVF medical advisory board (n = 11). Intervention(s): Donated embryos or donor oocyte/donor sperm embryos were provided to patients with backgrounds and physical attributes compatible with the embryonic phenotype. In some of the cycles, fresh ET was performed, with embryos shared among two, three, or four couples (n = 18); in other cycles, embryos were cryopreserved and transferred later (n = 21). Main Outcome Measure(s). Clinical and ongoing-delivered pregnancy rates. Result(s): The mean (±SD) numbers of embryos for cycles in which fresh ET and frozen ET was performed were 3.1 ± 0.7 (range, 2–5) and 3.6 ± 0.2 (range, 3–5), respectively. The clinical and ongoing-delivered pregnancy rates were 44.4% (8/18) and 33.3% (6/18), respectively, for cycles in which fresh ET was performed and 57.1% (12/21) and 47.6% (10/21), respectively, for cycles in which frozen ET was performed. Conclusion(s): Embryo donation is an alternative approach to assisted reproduction that meets the needs of single and lesbian women as well as older and less affluent couples. It is a cost-effective and efficacious means of achieving pregnancy.

Hydrosalpinges have been associated with poor in-vitro fertilization (IVF) outcome in some, but not all, studies, perhaps through endometrial effects. To determine whether hydrosalpinges affect IVF outcome via endometrial factors alone, we analysed the results of recipients of donor oocytes with hydrosalpinges, thereby controlling for confounding variables, while isolating the intrauterine environment. We retrospectively analysed 110 patients who underwent 121 donor oocyte cycles in a university-based assisted reproduction programme. Thirteen cycles involving recipients (n = 10) with hydrosalpinges were compared to 108 cycles involving recipients (n = 100) without hydrosalpinges. Pregnancy, implantation, miscarriage, and ectopic pregnancy rates were compared between women with and without hydrosalpinges. There were no significant differences between the hydrosalpinx and no hydrosalpinx groups with respect to donor age, recipient age, or number or grade of embryos transferred. Patients with a hydrosalpinx had significantly lower embryo implantation rates (7.1 versus 19.3%, P < 0.05) and significantly higher miscarriage (75.0 versus 14.9%, P < 0.05) and ectopic pregnancy rates (33.3 versus 0.0%, P < 0.05) than normal controls. We conclude that the presence of a hydrosalpinx adversely affects early pregnancy events by altering the intrauterine environment.

Previous studies have shown that transtubal dissemination of both fluid and malignant cells can occur during sonohysterography in patients with endometrial cancer, but the viability of these cells is unknown. This prospective study evaluated the occurrence of transtubal spill at laparotomy in patients with endometrial adenocarcinoma during sonohysterography and determined whether the spill volume was critical, and the disseminated cancer cells were viable. The participants were 16 evaluable patients with clinical stage I-IIA endometrial adenocarcinoma who underwent surgical treatment for endometrial carcinoma. The volumes required to obtain an adequate sonohysterography and at which tubal spill occurred were recorded. After processing and incubation of the collected specimens, the cells were examined for viability and cytologic analysis was performed. During adequate sonohysterography, the median volume that was required to perform sonohysterography was 8.5 ml (overall range, 1-90 ml; interquartile range, 5-21 ml). Of the 16 patients evaluated, 5 (31%; 95% confidence level CI, 14%-56%) had a transtubal spill at volume values between 1 and 20 ml of instilled saline solution. After an additional saline flush, the median total volume at which transtubal spill occurred was 20.5 ml (interquartile range, 9 ml to no spill [range: 1 to >140 ml]). The median total spill volume (20.5 ml) was more than twice that required for performance of an adequate sonohysterography (8.5 ml). There was no critical spill volume at which tubal spill occurred. Viable benign cells were disseminated in two patients (12.5%), and nonviable adenocarcinoma cells were identified in one patient (6.25%). These findings suggest that sonohysterography poses a low risk of transtubal dissemination of viable cancer cells. To the authors' knowledge, this is the first published study to examine cells for viability.

Our purpose was to survey recipients in an ovum donation program and report on their expectations while waiting for their potential donor recipient match.Accepted or rejected anonymous ovum donor matches (n = 80) from January 1996 to May 1997 were evaluated. Patients generated a "wish list" of desired traits and physical characteristics. From an approved donor pool of medically and psychologically screened women, candidates were drawn upon as potential matches and presented to the potential recipient, who decided whether to accept the donor. Reasons for accepting or rejecting the donor were tallied and were compared to the patient's wish list.Medical history and race were ranked by 33 and 23% of recipient couples as the two most important characteristics, while 74 and 54% stated that these were among the three most important factors in a potential donor compared with other traits. Fifty-seven (71%) recipients accepted, while 23 (29%) rejected, the first donor presented to them. Eleven were subsequently given a second choice within 6 months, with 10 (91%) accepting the next presented match. Recipients waiting for a donor were just as likely to accept or reject a potential candidate whether waiting3 months (33%; 15/46), 3-6 months (25%; 4/16), or6 months (22%; 4/18) (P0.05; NS). In all but five recipients, the reason for rejection was consistent with their top three priorities reported in their wish list.Phenotypic, ethnic, educational, and other interests are important in the selection of an ovum donor. Recipients are proactive in their decision process, making educated and well considered decisions in spite of the limited pool and the extended time frame in waiting for an appropriate ovum donor.

The first successful oocyte donation was performed to treat infertility in a patient whose partner was azospermic and had failed previous trials of in- rauterine insemination using donor sperm.1 Since then the indications for ovum donation have evolved to include a large number of clinical conditions. More than 6,300 ovum donation cycles have been reported in the English literature2–120 since Trounson’s first publication in 1983, and the primary indications now include premature ovarian failure, incipient ovarian failure, inheritable conditions, and physiologic menopause. Increasingly, oocyte donation is also used in patients who have failed multiple attempts at in vitro fertilization and embryo transfer (IVF-ET). Less frequently, it has also been recommended for patients with inaccessible ovaries and ovarian resistance syndrome. Table 2.1 lists the indications and the number of reported cases, and Figure 2.1 reflects each indication as a percentage of the total number of cases reported. This chapter discusses each indication and its significance to oocyte donation.

Conservative medical management of ectopic gestations may be difficult in patients with elevated levels of beta-hCG and cardiac activity. This case highlights the difficulty of managing such patients. Doppler flow studies and serum P, if available, should be used and can help determine those patients requiring repeated dosing of methotrexate. Patients using donor gametes and hormonal supplementation who subsequently develop an ectopic gestation may experience "rebound" ovulation, which further clouds the clinical picture. Careful follow-up using serial blood testing and ultrasound study is essential in the correct interpretation of a potentially confusing clinical picture.