Eldon D. Schriock

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles

OBJECTIVE To determine if the level of serum P drawn on the day of hCG administration predicts assisted reproductive technology (ART) outcome in patients undergoing stimulation with hMG under GnRH agonist (GnRH-a) suppression. DESIGN Retrospective P assay of stored serum. PATIENTS One hundred seventy-one patients (189 cycles) who had undergone GnRH-a suppression (leuprolide acetate or nafarelin) and stimulation with hMG for an ART procedure. MAIN OUTCOME MEASURES Progesterone RIA of serum obtained on the day of hCG administration. Measurement of sequential serum LH values by RIA in those patients with the highest P levels. RESULTS Pregnancy rates per oocyte retrieval were not correlated with the P level before hCG administration. There were 18 of 54 (33.3%) clinical pregnancies in those cycles with P < 0.9 ng/mL (conversion factor to SI unit, 3.180) and 42 of 135 (31.1%) clinical pregnancies in cycles with a P > or = 0.9 ng/mL. Significantly higher serum E2 levels and numbers of of follicles and oocytes obtained were observed in the high P cycles. There were no differences in the number of oocytes fertilized, the number of embryos transferred, or the implantation rate. However, a significantly higher percentage of mature oocytes were fertilized in the low P cycles (73%), as compared with the high P cycles (60%). CONCLUSIONS Serum P levels before hCG administration do not predict the outcome of ART cycles in patients suppressed with GnRH-a before hMG stimulation. Lower fertilization rates observed in the high P cycles did not have an effect on clinical outcome.

Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin) *

Administration of superactive agonistic analogs of gonadotropin-releasing hormone (GnRH) has been shown to induce a paradoxic and reversible suppression of gonadotropins, resulting in suppressed gonadal steroid concentrations. Because there currently is no uniformly successful and acceptable medical therapy for endometriosis, we examined the effects of 6 months of nasal administration (500 micrograms every 12 hours) of the agonistic analog of GnRH, nafarelin, on clinical signs and symptoms and hormonal profiles in eight women with endometriosis. All patients had prompt and near-complete relief from their painful symptoms of endometriosis. Laparoscopy or laparotomy, performed both before and after treatment in seven of the women, revealed complete resolution of active endometriotic lesions in five patients and only a single, small cul-de-sac implant in a sixth woman. A large ovarian endometrioma decreased slightly in response to treatment in the seventh woman. Serum luteinizing hormone and follicle-stimulating hormone concentrations, after a transitory stimulation at the onset of treatment, declined and were suppressed (P less than 0.001) during the remainder of treatment. Serum estradiol concentrations fell to approximately menopausal levels (less than 30 pg/ml) after 1 to 4 weeks. Reversibility of drug effect was prompt, with ovulatory menses returning 47 +/- 8 days (+/- standard deviation) after treatment. Thus, nasal administration of agonistic analogs of GnRH may represent a new treatment modality for endometriosis.

Birth after intracytoplasmic sperm injection with use of testicular sperm from men with kartagener/immotile cilia syndrome

OBJECTIVE To describe two cases of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with testicular sperm in men with immotile cilia syndromes. DESIGN Case report. SETTING A university-based male infertility clinic and assisted reproduction unit. PATIENT(S) Two couples with male factor infertility due to Kartagener/immotile cilia syndrome. INTERVENTION(S) IVF/ICSI with testicular sperm. MAIN OUTCOME MEASURE(S) Semen characteristics, sperm viability, fertilization rate, and pregnancy. RESULT(S) With testicular sperm, the two pronuclear fertilization rates were 63% and 60% in two cases. One case resulted in the birth of normal healthy girl. CONCLUSION(S) With testicular sperm, successful oocyte fertilization after ICSI in couples with male Kartagener/immotile cilia syndrome is possible despite the lack of sperm motility.

Gynecologic masses: Value of magnetic resonance imaging

Forty-two women with gynecologic abnormalities were studied with the use of magnetic resonance imaging. Magnetic resonance imaging correctly assessed the origin of the pelvic mass in all patients. In the evaluation of leiomyoma, magnetic resonance imaging accurately depicted the number, size, and location of the lesion. In the evaluation of endometrial carcinoma, magnetic resonance imaging depicted the location of the lesion, the presence of cervical extension, and the depth of myometrial penetration in the majority of the cases. In the analysis of adnexal cysts, magnetic resonance imaging was sensitive in localizing the lesion and was able to distinguish serous from hemorrhagic fluid. This preliminary report indicates that magnetic resonance imaging may become a valuable imaging modality in the diagnosis of gynecologic abnormalities.

Outcomes of natural cycles versus programmed cycles for 1677 frozen-thawed embryo transfers

The study compares outcomes for patients with frozen embryos who had frozen-thawed embryo transfer (FET) timed to their natural ovulation cycle versus cycles in which endometrial timing was programmed with oestrogen and progesterone. A total of 1205 patients undergoing 1677 FET cycles between 1 January 2000 and 31 December 2006 were analysed. Comparisons were made for patients undergoing modified natural versus programmed FET cycles, as well as between patients using their own eggs for frozen embryos versus those using donor-egg-derived embryos. Clinical pregnancy (gestational sac on 7 week ultrasound) rates (CPR), as well as miscarriage rates, were significantly higher in programmed FET cycles in patients using their own eggs (106/262, 40.5% per embryo transfer, P = 0.015) However, there was not a difference in delivered pregnancies between cycle types in own egg patients (natural cycle delivery rate 245/862, 28.4%; programmed cycle delivery rate 77/262, 29.4%). Furthermore, CPR were not different in natural (38/129, 29.5%) versus programmed cycles (144/424, 34.0%) for ovum donor recipients, nor were delivered pregnancy rates different in natural (33/129, 25.6%) versus programmed cycles (114/424, 26.9%) for ovum donor recipients. In conclusion, there is no significant difference in delivery rates for FET in natural (278/991, 28.1%) versus programmed (191/686, 27.8%) cycles using both own embryos and donor-egg-derived embryos.

Ablation of folliculogenesis in women by a single dose of gonadotropin-releasing hormone agonist: significance of time in cycle *

Effects of single subcutaneous doses (1, 5, 20, and 100 micrograms) of nafarelin, a potent gonadotropin-releasing hormone agonist, on the physiologic events of the human menstrual cycle were studied in 28 normal women. Nafarelin entered the circulation rapidly after injection. Peak concentrations were observed within 1 hour, and the plasma half-life was 4 to 5 hours. Maximal concentrations of luteinizing hormone and follicle-stimulating hormone were reached 3 to 4 hours after nafarelin administration. The magnitude of the gonadotropin responses depended both on the phase of the menstrual cycle (smallest responses during the early follicular phase) and the dose of nafarelin. Nafarelin administration during the early follicular phase delayed ovulation by 4.6 +/- 1.7 (standard deviation) days and prolonged the duration of the menstrual cycle from a pretreatment length of 29.2 +/- 2.1 days to 33.4 +/- 4.0 days (P less than 0.001). When nafarelin was administered shortly before or after ovulation, cycle length was not altered consistently. Administration 5 to 10 days after ovulation resulted in a truncated luteal phase. These observations suggest that the hormonal events triggered by nafarelin during the early follicular phase temporarily arrest the process of selection of the dominant follicle. Repeated intermittent administration of nafarelin or other gonadotropin-releasing hormone agonists in the early follicular phase may prevent follicular maturation and ovulation and may be a practical approach to contraceptive development.

Hyperglycemia and hyponatremia during operative hysteroscopy with 5% dextrose in water distention

Operative hysteroscopy may result in profound hyperglycemia and hyponatremia when crystaloids containing glucose are used as a distention medium. Four patients undergoing operative hysteroscopy developed hyperglycemia in proportion to increasing operative time. None of five monitored patients undergoing diagnostic hysteroscopy developed clinically significant hyperglycemia.

Elevated ovarian follicular fluid stem cell factor concentrations are associated with improved pregnancy rates in in-vitro fertilization cycles

OBJECTIVE To determine whether ovarian follicular fluid (FF) stem cell factor concentrations are associated with successful IVF pregnancies. DESIGN Nested case-control design evaluation of stem cell factor levels from the FF of oocytes fertilized and transferred after controlled ovarian hyperstimulation. SETTING University-based ART program. PATIENT(S) Infertile women undergoing IVF in a university-based ART program. INTERVENTION(S) Fifty-seven FF samples from a cohort of patients (n = 13) with tubal factor and unexplained infertility were stored at -80 degrees C and subsequently evaluated for stem cell factor concentration. Patients with endometriosis, polycystic ovary disease, and male factor infertility were excluded. Stem cell factor concentrations were measured using a commercially available ELISA kit according to the manufacturers specifications. The groups were analyzed using a one-way analysis of variance, and significance was determined using the chi2 analysis of contingency table, the unpaired t-test, or the Mann-Whitney rank-sum test. MAIN OUTCOME MEASURE(S) FF stem cell factor concentration, pregnancy. RESULT(S) Stem cell factor concentrations were significantly higher in the FF of the patients who achieved successful pregnancies than in those who did not (641.7+/-75.2 pg/mL versus 475.5+/-50.58 pg/mL). CONCLUSION(S) Elevated FF stem cell factor concentrations are associated with an increased likelihood of IVF success. Therefore, stem cell factor may play a role in human follicular and oocyte development, and increasing infrafollicular stem cell factor concentrations may improve pregnancy rates after oocyte retrieval, fertilization, and ET.

Enhanced post-receptor insulin effects in women following dehydroepiandrosterone infusion.

OBJECTIVE: We hypothesized that intravenous dehydroepiandrosterone (DHEA) would de crease insulin resistance in normal and insulin-resistant women. METHODS: Five insulin-resistant women diagnosed as having polycystic ovaries (PCO) with elevated testosterone and normal dehydroepiandrosterone sulfate (DHEAS) with amenorrhea were recruited. Obese controls (OC) with normal menses and normal testosterone and DHEAS were recruited and matched to each PCO woman for age and weight. The PCO women had a mean testosterone of 3.2 ± 0.4 nmol/L, fasting serum insulin level of 330 ± 55 pmol/L, and DHEAS level of 3.4 ± 1.3 μmol/L. An oral glucose tolerance test (OGTT) was performed at 8 AM after an overnightfast. A DHEA infusion (1 mg/hour for 17 hours) was begun at 6 PM and continued until the completion of the second OGTT performed the following morning at 8 AM. T-lympho cytes were drawn at 8 AM each morning. RESULTS: The DHEA infusion had no significant effect on any of the in vivo indices of insulin sensitivity, ie, basal and OGTT insulin, C-peptide, and ratios of insulin/glucose. In vitro, DHEA significantly increased insulin binding to T-lymphocytes of PCO women but caused no significant change in OC women. There was, however, marked enhancement of T-lymphocyte pyruvate dehydrogenase (PDH) activities in both groups of study subjects following DHEA. CONCLUSION: We conclude that a 17-hour infusion of DHEA enhanced T-lymphocyte insulin binding and PDH activity while producing no detectable improvements in in vivo indices of insulin sensitivity. (J Soc Gynecol Invest 1994;1:74-8)

Effect on corpus luteum function of luteal phase administration of a potent gonadotropin-releasing hormone analog (nafarelin)*

Fourteen women with ovulatory menstrual cycles were treated with a superactive agonistic analog of gonadotropin-releasing hormone (6-D-[2-naphthyl]-alanyl)-GnRH (nafarelin). Eight of the women received a single subcutaneous injection of nafarelin during the luteal phase at a dosage of 2, 5, or 100 micrograms for determination of the dose-response and pharmacokinetic characteristics of the drug. All doses stimulated the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Maximal release was obtained with the 5-micrograms dose (mean +/- standard deviation: delta LH = 297 +/- 75 mIU/ml; delta FSH = 29 +/- 7 mIU/ml), and there was no greater release of gonadotropin with the 100-micrograms dose. To investigate the contraceptive potential of nafarelin as a luteolytic agent, six of the women were treated with 100 micrograms of analog by daily injection for 10 days, beginning either 2 to 3 days or 5 to 7 days after ovulation. Gonadotroph desensitization or down-regulation developed within 24 hours, but serum concentrations of LH and FSH did not fall below normal values during treatment. There were no significant changes in mean estradiol or progesterone concentrations. There also was no change in mean length of the luteal phase (13.7 +/- 2.1 days [control] versus 13.6 +/- 1.4 days). Thus, nafarelin, like other superactive analogs of GnRH, does not appear to be clinically useful as a luteolytic agent in contraceptive development.