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Biomedical subjects

D Navot

Publications and source records attributed to D Navot.

At least 19 recordsLinked to original sources

Endometrial thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation.

OBJECTIVE: To determine if ultrasonographic endometrial pattern or thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation. DESIGN: Ultrasonographic endometrial thickness and pattern were determined and compared with histologic assessment of endometrial maturation. PATIENTS: Forty-six women underwent 52 preparatory cycles for ovum donation. Transvaginal ultrasound (US) was performed after 14 days of E2 replacement and, after 12 days of P, an endometrial biopsy was performed. In 12 cycles, a continuous dose of 2 mg/d E2 was administered. In cycles with out-of-phase biopsies (dated earlier than day 24) and in the last 34 cycles, all women received an escalating dose of E2 before initiation of P. Additionally, the 46 women underwent 55 ETs with USs performed on cycle day 15. RESULTS: Six women had abnormal biopsies in their first preparatory cycle on the continuous E2 protocol, which normalized with the escalating protocol. All other women had normal biopsies. Women with abnormal biopsies had significantly thinner endometrium (< or = 6 mm) but similar endometrial patterns compared with women with normal biopsies. In women having US in preparatory and transfer cycles, there were no differences in endometrial thickness or pattern between examinations. CONCLUSIONS: Endometrial thickness > or = 7 mm in hormone replacement cycles predicts in phase endometrial histology and can replace the endometrial biopsy.

Biopsy

Evaluation of the reproductive performance of women with elevated day 10 progesterone levels during ovarian reserve screening.

OBJECTIVES: To evaluate the relationship of elevated day 10 P levels (> or = 1.1 ng/mL, conversion factor to SI unit, 3.18) during ovarian reserve screening and reproductive performance. DESIGN: Prospective screening with longitudinal follow-up. INTERVENTIONS: One hundred seven women underwent ovarian reserve screening with a clomiphene citrate challenge test. MAIN OUTCOME MEASURES: Serum FSH, LH, and E2 levels were determined on cycle day 3 and FSH, LH, and P levels were determined on day 10. A fertility evaluation was completed and a treatment plan was instituted. RESULTS: Twenty-two of 107 (20.6%) women had day 10 P levels > or = 1.1 ng/mL. Women with elevated day 10 P levels were similar in age to women with normal day 10 P levels (< or = 0.9 ng/mL) but had significantly shorter menstrual cycles, higher day 3 and day 10 FSH levels, higher day 3 E2 levels, and higher day 10 LH levels than women with normal day 10 P levels. During ovarian hyperstimulation, women with elevated day 10 P levels required more ampules of hMG, had lower peak E2 levels, and had fewer mature follicles than women with a normal day 10 P level. Sixteen of 85 (18.8%) women with normal day 10 P levels became pregnant, but none of the 22 women with elevated day 10 P levels became pregnant. The incidence of diminished ovarian reserve was higher in women with elevated day 10 P levels (13/22; 59%) when compared with women with a normal day 10 P levels (9/85; 10.6%). CONCLUSIONS: Elevated day 10 P levels (> or = 1.1 ng/mL) during ovarian reserve screening is associated with diminished ovarian reserve and correlates with menstrual cycle parameters associated with a short follicular phase and poor reproductive performance.

Adult

Relationship between circulating human chorionic gonadotropin levels and premature luteinization in cycles of controlled ovarian hyperstimulation.

OBJECTIVE: To determine if premature luteinization (serum P levels > 1.1 ng/mL on or before the day of hCG administration) during controlled ovarian hyperstimulation (COH) is associated with elevated levels of serum hCG. SETTING: Tertiary fertility center. DESIGN: Retrospective evaluation of ovum donors undergoing COH. PATIENTS: Forty-four women underwent COH. Comparisons of serum hCG levels and hormonal and cycle characteristics were made between cycles with premature luteinization (group I) and without premature luteinization (group II). RESULTS: Group I (16 women) were similar to women in group II in age, amount of hMG, and the ratio of FSH:hMG received. Both groups received hCG on similar days, but women in group I had higher peak E2 levels. Serum hCG levels increased and correlated with serum P levels in group I only and were higher on the day of hCG administration (group I 1.8 +/- 0.9 mIU/mL versus group II 1.2 +/- 0.45 mIU/mL; conversion factor to SI unit, 1.00). Peak E2 and LH levels, ampules of hMG and the FSH:LH ratio, and day of hCG administration did not correlate with hCG levels. Human chorionic gonadotropin exposure, as measured by area under the curve, was significantly higher in group I compared with group II. CONCLUSION: Higher serum levels of hCG and integrated hCG exposure are found in COH cycles with premature luteinization compared with cycles without premature luteinization. Higher hCG levels may be due to decreased clearance of hCG from the circulation and/or the hCG content of hMG.

Adult

Evaluation of the impact of concurrent gonadotropin-releasing hormone (GnRH) antagonist administration on GnRH agonist-induced gonadotrope desensitization.

OBJECTIVE: To evaluate the impact of chronic GnRH antagonist therapy on the extent of GnRH agonist-induced gonadotrope desensitization. DESIGN: Prospective and controlled. SETTING: Primate Research Center. PARTICIPANTS: Six reproductive age cycling female baboons (Papio cyanocephalus anubis). INTERVENTIONS: The animals were divided into two groups. Group A received a total of 19 pulses of 0.83 microgram/kg leuprolide acetate (LA) on a 12-hour dosing schedule. Group B received Nal-Lys (3 mg/kg then 1 mg/kg every other day) for 1 week and then added an identical 19 pulses of LA while continuing Nal-Lys therapy. MAIN OUTCOME MEASURES: Characterization of the gonadotropin response was done by collecting serum samples at -15, 0, 15, 30, 60, 90, 120, 240, and 480 minutes relative to the injection of the LA. RESULTS: After equivalent baseline responses, the baboons pretreated with Na-Lys had an increased LH and FSH response to the administration of the LA. After a total of 19 pulses of the LA, the Nal-Lys-treated animals had an increased FSH response in comparison to the untreated controls. This indicates that the extent of gonadotrope desensitization was reduced in the presence of the GnRH antagonist. CONCLUSIONS: The presence of GnRH antagonist reduces the extent of gonadotrope desensitization in response to the administration of repetitive pulses of GnRH agonist.

Animals

Embryo quality and pregnancy potential of fresh compared with frozen embryos--is freezing detrimental to high quality embryos?

To determine the effect of cryopreservation on embryo quality and the pregnancy potential of embryos, donated oocytes from the same donor (n = 24) were randomly allocated, with subsequent transfer to two or more different ovum recipients resulting in at least one fresh and one frozen embryo transfer cycle from the same cohort of oocytes. Endometrial receptivity was controlled in all ovum recipients, and male factor patients were excluded. The number of embryos transferred, mean embryo grade transferred, number of high quality embryos (grade < or = 2.5, grade 1 being best) transferred and embryo implantation and live birth rates are reported. Significantly more embryos (4.4 +/- 1.2 versus 3.3 +/- 1.2, P < 0.00003) of higher quality (1.9 +/- 0.5 versus 2.1 +/- 0.5, P < 0.013) and of a more advanced cell stage (3.0 +/- 0.6 versus 2.6 +/- 0.7, P < 0.019) were transferred fresh than after cryopreservation respectively. Implantation rates/embryo [19/151 (12.6%) and 9/111 (8.1%)] and live birth rates/transfer [11/42 (26.2%) and 6/45 (13.3%)], from fresh and frozen transfers respectively, were not significantly different despite the larger number of high quality embryos transferred fresh. Embryo cryopreservation adversely affects embryo quality, but does not have detrimental effects on the implantation or pregnancy potential of high quality embryos. Because of the loss of embryos during freeze-thawing during frozen embryo cycles, every effort should be made to attempt a fresh transfer.

Adult

Life table analysis of pregnancy rates in a general infertility population relative to ovarian reserve and patient age.

This study evaluated the impact of age and ovarian reserve status on cumulative pregnancy rates. Approximately 1200 women from a general infertile population underwent ovarian reserve screening with the clomiphene citrate challenge test in the first few months of their initial evaluation. All patients then underwent a thorough infertility evaluation with therapy appropriate for their specific diagnoses. Patients with evidence of tubal disease, peritoneal adhesive disease, or male factor were eliminated. The 588 remaining patients were evaluated based on their age and ovarian reserve status, and their long-term pregnancy rates were compared using life table analyses. There was a dramatic decrease in pregnancy rates associated with an abnormal clomiphene citrate challenge test which was uniformly poor independent of age. Patients with normal ovarian reserve had much higher pregnancy rates, but a significant age-related decline in pregnancy rates was clearly identified. We conclude that women with evidence of diminished ovarian reserve have uniformly poor pregnancy rates independent of their age, but that age remains an important prognostic factor among those with a normal ovarian reserve. The combined use of maternal age and ovarian reserve screening should be used when counselling individual patients regarding their long-term prognoses for conception.

Adult

Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation.

OBJECTIVE: To evaluate the contribution of the uterus to age-related reproductive failure in women. PATIENTS: Thirty-eight ovum donors (30.2 +/- 4.9 years [mean +/- SD]) donating oocytes throughout 102 ovum donations. Fifty-one cycles were documented in "younger" recipients (35.8 +/- 3.1 years) and 51 in "older" recipients (44.0 +/- 3.1 years). The study was prospectively designed; same-cohort oocytes obtained from one young donor during a specific cycle were evenly distributed between "young" and "old" ovum recipients. Use of oocytes from a single source and a unique ovulatory cohort provides strict control over oocyte quality. Uterine age is varied by design, according to the age of the recipient at the time of ET. The role of the aging uterus in the decline of female fertility can be thus isolated and scrutinized. RESULTS: No significant (NS) difference in the number of ova received (7.9 +/- 3.4 versus 7.0 +/- 3.5), ova fertilized (4.4 +/- 1.5 versus 4.5 +/- 2.3), or embryos transferred (4.1 +/- 1.5 versus 4.1 +/- 1.6) was observed between the < 40 and > or = 40 recipient age groups. A total of 23 pregnancies occurred among the 102 ETs (22.6%). Eleven clinical pregnancies (21.6%) resulting in 10 deliveries were observed in the < 40 recipient age group, and 12 clinical pregnancies (23.5%) leading to 10 deliveries occurred in the > or = 40 recipient age group (NS). The pregnancy loss rates were 9.1% (1 of 11) and 16.7% (2 of 12) for the two recipient age groups, respectively, (NS). CONCLUSION: The capacity to conceive and to gestate a conception to term when oocyte quality is controlled appears to be independent of uterine aging through the fifth decade of life.

Adult

Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization.

OBJECTIVE: To determine if women who previously had demonstrated poor ovarian responsiveness during ovulation induction for IVF would obtain an improved follicular response by the administration of microdoses of GnRH agonist (GnRH-a). DESIGN: Prospective evaluation using the same patients' previous assisted reproductive technology cycles as historic controls. SETTING: Large military tertiary care center. PATIENTS: Thirty four patients who were low responders (peak E2 < 500 pg/mL [conversion factor to SI unit, 3.67]) during ovulation induction with luteal phase GnRH-a suppression followed by exogenous gonadotropins. INTERVENTIONS: Follicular phase administration of 20 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and supplemented with exogenous gonadotropins beginning on cycle day 5. MAIN OUTCOME MEASURES: Paired analysis of initial E2 response, peak E2 level attained, number of follicles > or = 16 mm, duration of stimulation, ampules of gonadotropins required, late follicular LH levels, number of mature oocytes retrieved, and fertilization rates. RESULTS: Ovarian responsiveness was enhanced during the microdose GnRH-a stimulation cycle when compared with the previous stimulation cycle. Specifically, the patients had a more rapid rise in E2 levels, much higher peak E2 levels, the development of more mature follicles, and the recovery of larger numbers of mature oocytes at the time of retrieval. None of the patients had premature LH surges as evidenced by a significant rise in LH levels or a significant decline in E2 levels. There were no differences in the fertilization rates. CONCLUSION: Microdose GnRH-a administration beginning in the early follicular phase may result in an augmented ovarian response when compared with traditional GnRH-a-exogenous gonadotropin stimulations. Additionally, it may decrease gonadotropin requirements while effectively preventing premature LH surges.

Adult

Cigarette smoking accelerates the development of diminished ovarian reserve as evidenced by the clomiphene citrate challenge test.

OBJECTIVE: To test whether the reduced fecundity in women who smoke cigarettes may be attributed to the accelerated development of diminished ovarian reserve. DESIGN: Retrospective evaluation of clomiphene citrate (CC) challenge tests in women from a general infertility population who did and did not smoke cigarettes (part 1) and retrospective evaluation of the impact of smoking on pregnancy rates (PRs) in IVF among women with normal ovarian reserve (part 2). SETTING: Large military tertiary care center. PATIENTS: Sixty-five women who smoked cigarettes and 145 women who did not smoke cigarettes in the general infertility population (part 1) and women undergoing IVF for strict tubal factor infertility with normal ovarian reserve who did (n = 29) and did not (n = 73) smoke (part 2). INTERVENTIONS: Clomiphene citrate challenge tests, composed of FSH levels on cycle days 3 and 10 with 100 mg of CC administered on cycle days 5 through 9. MAIN OUTCOME MEASURES: Comparison of the incidence of abnormal CC challenge test results between women who did and did not smoke, and comparison of peak E2 levels, number of mature follicles, number of mature oocytes retrieved, fertilization rates, and total and ongoing PRs. RESULTS: The incidence of diminished ovarian reserve was increased in women who smoked (8 of 65 [12.31%]) when compared with age-matched controls who did not smoke (7 of 145 [4.83%]). Among women with normal CC challenge tests who were undergoing IVF, there were no differences in peak E2 levels, the number of mature follicles, the number of mature oocytes retrieved, fertilization rates, or total and ongoing PRs. CONCLUSION: Women who smoke have an accelerated development of clinically detectable diminished ovarian reserve. Additionally, the fact that women who smoke cigarettes with normal ovarian reserve have ovarian responses and PRs that are equivalent to age-matched nonsmoking controls suggests that diminished ovarian reserve may be a principal mechanism reducing fecundity among women who smoke cigarettes.

Adult

Infertile couples with normal counts who require subzonal sperm insertion possess a fertility defect that affects zona pellucida penetration.

The results of subzonal sperm insertion (SUZI) have been retrospectively analysed in a subset of patients with normal sperm counts who were found to require SUZI because of poor or absent fertilization of zona-intact oocytes. This patient group is of particular interest because male factor-related infertility cannot be due to insufficient numbers of spermatozoa reaching the oocytes. Thus, failed fertilization can be attributed to deficiencies in one or more steps in the fertilization process, and SUZI provides a method of distinguishing defects of zona pellucida penetration from gamete fusion. A total of 26 such patients were treated identically to and concurrently with a much larger group of SUZI candidates who typically suffered from oligozoospermia, and fertilization results were compared. Fertilization rates after SUZI were higher in patients with normal counts than in oligozoospermic patients (51 and 26% respectively), indicating that the proportion of spermatozoa capable of fusing with the oocyte is the same or higher in the group with normal counts. In addition, nearly all SUZI procedures led to fertilization (23/26), with two out of three failed fertilizations occurring in cases where two or less oocytes were manipulated, results which further indicate that failed fertilization in these patients is not due to a defect at the level of gamete fusion. These findings suggest that infertility in these patients is based upon the inability of the spermatozoa to reach the oolemma and thus, that their fertility defect resides at the step of zona penetration.

Adult

Immunohistochemical localization of transforming growth factor-beta in human implantation sites.

Transforming growth factor-beta (TGF beta), a protein known to antagonize many of the functions of the epidermal growth factor-receptor system, was localized immunohistochemically in unruptured ectopic pregnancies (EP) removed by salpingectomy (n = 8), uterine decidua from EP (n = 4), and decidua and trophoblast from electively terminated first trimester pregnancies (ETP; n = 8). Two rabbit polyclonal antisera that recognize both TGF beta 1 and beta 2 were used. Immunostaining for TGF beta was identified in all three forms of trophoblast, cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts, which were differentiated histologically and immunohistochemically. Moderate cytoplasmic immunostaining was found in villous cytotrophoblasts in both EP and ETP. Nonvillous (anchoring) cytotrophoblasts in these same tissues demonstrated moderate immunostaining adjacent to the villous and light immunostaining distal to the villous. In intermediate trophoblasts, moderate to intense immunostaining was seen in EP and ETP. Syncytiotrophoblasts demonstrated moderate cytoplasmic immunostaining in EP and ETP as well as moderate to intense staining of plasma membranes and microvilli. Nuclear staining was not evident in any form of trophoblast. TGF beta immunostaining was demonstrated in both glands and stroma of decidua from both EP and ETP; however, staining was more intense in decidua from ETP. With the known presence of TGF beta receptors and mRNA in placenta, these results suggest an autocrine/paracrine role for TGF beta regulation of endometrial-trophoblast function during human implantation.

Decidua

Gonadotropin-releasing hormone antagonist administration enhances gonadotrope responsiveness at doses inadequate to suppress immunoassayable gonadotropin levels.

Chronic GnRH antagonist therapy produces enhanced gonadotrope responsiveness to supraphysiologic stimuli despite the lack of any measurable suppression of gonadotropin levels. This indicates that GnRH antagonists fundamentally alter gonadotrope response mechanisms without inhibiting gonadotropin release. Beyond the physiologic implications, these data may eventually impact the development of clinical protocols. Benefits could include enhancements in the endogenous gonadotropin flare during controlled ovarian hyperstimulation cycles. Additionally, proposed contraceptive protocols where GnRH antagonists are used to produce the initial inhibition in gonadotropin release and are then followed by a GnRH-a (to avoid the gonadotropin flare) may in fact produce paradoxical results.

Animals

Analysis of factors contributing to success in a program of micromanipulation-assisted fertilization.

OBJECTIVE: To determine factors important to clinical success in micromanipulation-assisted in vitro fertilization (IVF). DESIGN: Procedures invoked in two separate series of micromanipulation-assisted IVF cycles, one unsuccessful (series I) and the other successful (series II), were compared in an effort to identify changes that led to clinical success. SETTING: University-based IVF clinic. PATIENTS: In both IVF series involving micromanipulation, patients consisted of infertile couples who fit any of five categories of male-factor related infertility. The female patients underwent controlled hyperstimulation for oocyte retrieval and the oocytes were inseminated normally or were subjected either to partial zona dissection or subzonal sperm insertion to assist fertilization. Results in all groups were compared between the two patient series. RESULTS: In the successful series II, a noticeable improvement in fertilization rate and embryo quality was observed compared with series I. A significant increase in the percentage of patients reaching embryo transfer, the pregnancy rate per transfer, and the pregnancy rate per retrieval were noted in series II; a 25% ongoing pregnancy rate per retrieval was observed overall in this successful group, with "ongoing" defined as manifestation of at least a fetal sac on ultrasound with no detectable problems. Patients with a mixed transfer of embryos derived from manipulated and normally inseminated oocytes had a 75% rate of pregnancy per transfer in series II. Differences between the two series could not be attributed to patient selection or biases in selection of oocytes relegated to micromanipulation. However, oocyte handling, micromanipulation, and culture protocols differed significantly between the two series in that temperature and pH of oocytes was better controlled, and micromanipulation time was minimized in series II. CONCLUSION: Success in micromanipulation depends on maintenance of the oocyte in a stable and supportive environment throughout the micromanipulation procedure. It is also important to minimize trauma to the eggs by performing micromanipulation rapidly and with minimal distortion of the egg. Patients with a poor fertilization rate in standard IVF may experience a substantial increase in the likelihood of pregnancy when micromanipulation-assisted fertilization is performed on some eggs.

Cleavage Stage, Ovum

Gonadotropin responsiveness to ultralow-dose leuprolide acetate administration in baboons.

OBJECTIVE: To evaluate the gonadotropin response to ultralow doses of a GnRH agonist, leuprolide acetate (LA). DESIGN: Prospective and cross-controlled. SETTING: Primate research center. SUBJECTS: Four reproductive age cycling baboons (Papio cyanocephalus). INTERVENTIONS: Three different doses of LA were given intravenously to each animal followed by serial sampling. MAIN OUTCOME MEASURES: Response patterns of circulating serum gonadotropin levels. RESULTS: All four animals responded to each of the three doses of LA in a dose-dependent fashion. Levels of LH and FSH peaked at 49.5 +/- 2.6 mIU/mL and 72.5 +/- 3.4 mIU/mL, respectively, for the highest dose studied (0.17 microgram/kg). Levels of LH peaked earlier but were lower than the FSH peak levels. CONCLUSIONS: Supraphysiological levels of gonadotropins are attained after the administration of ultralow doses of LA. The level of the response is dose-dependent and is in the range that is required to attain controlled ovarian hyperstimulation.

Analysis of Variance

Evaluation of the significance of the estradiol response during the clomiphene citrate challenge test.

OBJECTIVE: To evaluate the relationship between the E2 response during the clomiphene citrate (CC) challenge test and ovarian responsiveness to exogenous gonadotropins. DESIGN: Performance of a CC challenge test followed by ovulation induction with exogenous gonadotropins as part of participation in an assisted reproduction program. SETTING: Assisted reproduction program in a large military tertiary care center. PATIENTS: Two hundred forty-seven women between the ages of 24 and 39 years with normal CC challenge tests within 1 year of their assisted reproduction cycle. INTERVENTIONS: Performance of CC challenge tests and ovulation induction with exogenous gonadotropins as a component of an assisted reproduction cycle. MAIN OUTCOME MEASURES: Correlation of the E2 response during the CC challenge test and peak E2, the duration of stimulation, number of ampules of exogenous gonadotropins, number of mature follicles, number of mature oocytes recovered, and fertilization and pregnancy rates in an assisted reproduction program. RESULTS: No correlation exists between the E2 response during the CC challenge test and any of the parameters evaluated. CONCLUSION: Monitoring of the E2 response during the CC challenge test did not predict ovarian responsiveness or pregnancy rates in patients participating in an assisted reproduction program and one may choose not to include it in routine testing.

Adult

Premature luteinization in controlled ovarian hyperstimulation has no adverse effect on oocyte and embryo quality.

OBJECTIVE: To determine if premature luteinization has an adverse effect on oocyte and, hence, embryo quality. DESIGN: Retrospective evaluation of anonymous ovum donors/oocyte recipients. SETTING: A large oocyte donation program. PATIENTS, PARTICIPANTS: Sixty-eight women undergoing controlled ovarian hyperstimulation (COH) as ovum donors were matched to 68 women with ovarian failure as ovum recipients who had endometrial maturation exogenously controlled by an identical hormone replacement protocol. INTERVENTIONS: Serum was collected for E2 and P in donors and recipients. MAIN OUTCOME MEASURES: The incidence of premature luteinization was determined in donors. Cycle characteristics were compared between donors with and without premature luteinization, with emphasis on oocyte and embryo quality. Implantation rates per embryo and delivery rates per transfer were measured in recipients. RESULTS: Twenty-one (31%) of the donors demonstrated premature luteinization. Serum P was higher on day before hCG, day of hCG, and day after hCG in women demonstrating premature luteinization. However, there were no differences between donor cycles with or without premature luteinization as determined by donor age, ampules of gonadotropins used, day of hCG administration, peak E2, total number of oocytes, and number of mature oocytes retrieved. Ovum recipients were of similar age and had similar E2 exposure (area under the E2 curve) before P administration. Similar fertilization rates, incidence of polyspermia, number of embryos transferred of similar embryo grade, and similar implantation rates and deliveries per transfer were observed in women receiving oocytes from donors with and without premature luteinization, respectively. CONCLUSIONS: Similar oocyte quality, fertilization, and polyspermia rates, embryo quality, implantation, and delivery rates suggest that any negative impact of premature luteinization on pregnancy rates in COH cycles from young women is not due to an adverse effect of PL on oocyte and hence embryo quality, but rather on the endometrial environment.

Chorionic Gonadotropin

Premature luteinization is not eliminated by pituitary desensitization with leuprolide acetate in women undergoing gonadotrophin stimulation who demonstrated premature luteinization in a prior gonadotrophin-only cycle.

A total of 40 women who demonstrated premature luteinization (serum progesterone > or = 3.5 nmol/l (1.1 ng/ml) on or before the day of human chorionic gonadotrophin (HCG) administration) during ovarian stimulation with human menopausal gonadotrophins (HMG) were restimulated in 46 subsequent cycles after pituitary desensitization with the gonadotrophin-releasing hormone agonist (GnRHa, 1 mg), leuprolide acetate. Five women were treated with a double dose of agonist (2 mg) when premature luteinization was determined on the single dose protocol. In HMG-only cycles, a frank luteinizing hormone (LH) surge was detected in 30 cycles; 15 cycles were cancelled because of premature ovulation. In agonist cycles there were no cancellations, although 25 cycles demonstrated premature luteinization and in six cycles a frank LH surge was detected. Doubling the dose of the agonist did not prevent premature luteinization. Agonist cycles with and without premature luteinization did not differ in any in-vitro fertilization (IVF) outcome parameters (ampoules of gonadotrophins, day of HCG administration, peak oestradiol concentration, number of oocytes retrieved, fertilized, transferred or cryopreserved). We conclude that in patients who demonstrate premature luteinization in a gonadotrophin-only cycle, pituitary desensitization may not completely eliminate subtle luteinization or a frank LH surge.

Chorionic Gonadotropin