Low dose human chorionic gonadotropin administration at the time of gonadotropin releasing-hormone agonist trigger versus 35 h later in women at high risk of developing ovarian hyperstimulation syndrome - a prospective randomized double-blind clinical trial.

BACKGROUND: Ovarian hyperstimulation syndrome remains a serious complication during in vitro fertilization cycles if high dose human chorionic gonadotropin (hCG) is used to trigger ovulation in high responder patients. Though much of this risk is mitigated with trigger using gonadotropin releasing-hormone (GnRH) agonist alone, it may result in lower birth rates. GnRH-agonist trigger and adjuvant low dose hCG has been proposed to improve birth rates, but timing of this hCG support to corpus luteum function has never been fully described. In this randomized, prospective trial, we explore differences in live birth rates and incidence of ovarian hyperstimulation syndrome (OHSS) in high-responder patients undergoing in vitro fertilization (IVF) receiving low dose hCG at the time of GnRH-agonist (dual trigger) or hCG adjuvant at the time of oocyte retrieval. Does the timing of hCG support make a difference? RESULTS: Thirty-four subjects high-responder patients were randomized to receive low-dose hCG at the time of GnRH-agonist trigger (Group 1) and 37 received low-dose hCG at the time of oocyte retrieval (Group 2). There were no differences in the baseline characteristics and outcome of ovarian stimulation between the two groups. There were no differences in the live birth rates between Group 1 and Group 2 by intention-to-treat (14/34, 41.2% versus 21/37, 56.8%, p = 0.19) or per-protocol (14/26, 53.8% versus 19/31, 61.3%, p = 0.57) analyses. There was a slightly higher incidence of OHSS in Group 2 compared to Group 1 although the difference was not statistically significant (3/31, 9.7% versus 1/26, 3.8%). All the cases of OHSS in Group 2 were moderate while the one case of OHSS in Group 1 was mild. CONCLUSIONS: For high responder patients receiving GnRH-agonist trigger, low dose hCG supplementation allowed high pregnancy rates after fresh embryo transfer, regardless of whether it was given at the time of trigger or at oocyte retrieval. Dual trigger may be preferable to reduce the risk of OHSS.

Predicting successful induction of oocyte maturation after gonadotropin-releasing hormone agonist (GnRHa) trigger.

STUDY QUESTION: Are there factors predicting the number of total and mature oocytes retrieved after controlled ovarian hyperstimulation (COH) utilizing a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist (GnRHa) to induce oocyte maturation? SUMMARY ANSWER: Peak estradiol (E2) level, post-trigger LH and progesterone and the magnitude of LH rise are independent predictors of the total number of oocytes and mature oocytes retrieved. WHAT IS KNOWN ALREADY: Despite multiple follicular development in high responders, oocyte retrieval after a GnRHa trigger in a small subset of patients fails to obtain a substantial number of total oocytes or mature oocytes. STUDY DESIGN, SIZE AND DURATION: A retrospective chart review of all autologous and oocyte donation cycles utilizing a GnRHa antagonist protocol where GnRHa was used for the induction of oocyte maturation between 1 April 2003 and 31 December 2011. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A total of 508 autologous and donor IVF/ICSI cycles utilizing a GnRH antagonist protocol for COH and GnRHa for the induction of oocyte maturation at a university-based tertiary fertility center. MAIN RESULTS AND THE ROLE OF CHANCE: Peak E2 on the day of trigger (r = 0.19, P < 0.001), post-trigger LH (r = 0.12, P = 0.009) and progesterone (r = 0.47, P < 001) and LH rise (r = 0.18, P < 0.001) all positively correlated with the number of total and mature oocytes retrieved. The true incidence of empty follicle syndrome was 1.4% (7/508). There was no post-trigger LH or progesterone cut-off value for the prediction of oocyte yield. However, all cases of empty follicle syndrome occurred in patients with post-trigger LH <15 IU/l and P ≤ 3.5 ng/ml. The findings of this study may also be due to chance since it was a retrospective study and not prospectively designed. LIMITATION, REASONS FOR CAUTION: This is a retrospective chart review and therefore subject to bias. Serum hormone measurements were performed between 8 and 12 h after GnRHa trigger rather than a standardized time period following trigger administration. Therefore, peak levels of LH may have been missed due to the short ascending limb of LH rise lasting approximately 4 h after GnRHa trigger. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study can be generalized to high responders utilizing a GnRH antagonist protocol for COH and a GnRHa for the induction of oocyte maturation. The use of alternative stimulation regimens or medications will limit the ability to generalize the results of this study to other populations. STUDY FUNDING/COMPETING INTEREST(S): This study was not funded, and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: n/a.

Should Cochrane reviews be performed during the development of new concepts?

Cochrane reviews are internationally recognized as the highest standard in evidence-based health care. A Cochrane analysis conducts systematic reviews of primary research in human health care, and the analysis includes a comprehensive search of all potentially relevant studies and the use of explicit, reproducible criteria in the selection of studies for review. Thus, Cochrane reviews, undoubtedly provide many useful clinical guidelines. In this opinion paper, however, it is questioned at what level of clinical development of a new strategy a Cochrane review should be conducted in order not to draw premature conclusions that may not be sustained later on. Previous examples of this are debated together with the most recent Cochrane review regarding GnRH agonist triggering of final oocyte maturation, in which debatable conclusions are drawn from early studies, when the concept was still under development. We question the current policy of meta-analysis and recommend that in the future, the meta-analysts should await the results of a sufficient number of well-performed studies with an established new regime before an analysis is performed in order to avoid too early and possibly biased conclusions.

GnRH agonist to induce oocyte maturation during IVF in patients at high risk of OHSS.

The aim of this retrospective study was to evaluate the effectiveness of gonadotrophin-releasing hormone agonist (GnRHa) to trigger oocyte maturation in patients with polycystic ovarian syndrome (PCOS) or previous high response. The outcome of ovarian stimulation and IVF in patients using GnRHa to trigger oocyte maturation after co-treatment with GnRH antagonist (study group) was compared with patients using human chorionic gonadotrophin (HCG) to trigger oocyte maturation after a dual pituitary suppression protocol with oral contraceptive pill (OCP) and GnRHa overlap (control group). All patients received intramuscular progesterone for luteal support but patients in the study group received additional supplementation with oestradiol patches. The mean number of oocytes, proportion of mature oocytes and fertilization rate were similar between the study and control groups. Implantation rate (38.6% versus 45.1%), clinical pregnancy rate (69.6% versus 60.9%) and delivery rate (62.5% versus 56.5%) were similar in the study and control groups respectively. There was one case of moderate ovarian hyperstimulation syndrome (OHSS) in the control group and none in the study group. GnRHa is effective in triggering oocyte maturation in patients with PCOS or previous high response. Further randomized studies are required to evaluate its effectiveness in the prevention of OHSS in this group of patients.

Intracytoplasmic sperm injection overcomes previous fertilization failure with conventional in vitro fertilization.

OBJECTIVE: To evaluate the outcome of intracytoplasmic sperm injection (ICSI) in patients with previous idiopathic fertilization failure (< or =20% fertilization rate) after conventional IVF. DESIGN: Retrospective analysis. SETTING: IVF program at a university medical center. PATIENT(S): Twenty-five patients who underwent 38 ICSI cycles after experiencing unexplained fertilization failure with conventional IVF (group A) and 87 patients who underwent 118 ICSI cycles for male factor indications during the same period (group B). INTERVENTION(S): Intracytoplasmic sperm injection was performed in a subsequent cycle after fertilization failure with conventional IVF. MAIN OUTCOME MEASURE(S): Outcomes of IVF were compared between groups A and B. RESULT(S): Fertilization was achieved with ICSI in all patients with previous fertilization failure. The mean (+/- SD) fertilization rate (68%+/-21% vs. 64%+/-22%), implantation rate per embryo (22.6% vs. 20%), and delivery rate per cycle (47.3% vs. 49.1%) did not differ significantly between groups A and B. Overall, 72% of patients with previous unexplained fertilization failure had a successful pregnancy after ICSI. CONCLUSION(S): Intracytoplasmic sperm injection can overcome unexplained fertilization failure caused by a potentially occult gamete abnormality, with the same fertilization, implantation, and pregnancy rates as are seen in patients with abnormal sperm parameters.

In vitro fertilization following conservative management of stage 3 serous borderline tumor of the ovary.

Among patients with advanced stage serous borderline tumors of the ovary, those with micropapillary architecture or invasive implants have the greatest risk of malignant transformation. In the absence of these patterns, consideration can be given to preservation of reproductive function. A 28-year-old, nulliparous patient presented with symptoms mimicking advanced ovarian cancer. Histology showed a serous borderline tumor with a hierarchical branching pattern. Surgery was able to remove all visible disease but still preserve the uterus and a portion of one ovary. She subsequently underwent in vitro fertilization and delivered a full-term infant.

Withholding gonadotropin administration is an effective alternative for the prevention of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the outcomes of IVF and the incidence of ovarian hyperstimulation syndrome (OHSS) after discontinuing gonadotropin therapy in patients at risk of developing OHSS by delaying hCG administration until a drop in serum E2 levels was observed. DESIGN: Retrospective study. SETTING: IVF program at a university center. INTERVENTIONS: Gonadotropin administration was withheld in 22 patients (group 1) when their serum E2 level was > or = 3,000 pg/mL (conversion factor to SI unit, 3.671). Patients continued GnRH analogue injections daily, and hCG was administered when serum E2 levels dropped to < or = 3,000 pg/mL. Outcomes were compared with 26 patients (group 2) in whom embryo transfer was canceled and all embryos cryopreserved for transfer during a subsequent unstimulated cycle. MAIN OUTCOME MEASURES: Outcomes of IVF and incidence of OHSS were compared in both groups of patients. In group 1, follicular and hormonal parameters before and after the coasting interval were compared in pregnant versus nonpregnant patients. In addition, serum hormonal profiles were evaluated daily during the coasting period to determine the effects of gonadotropin withdrawal. RESULTS: Although the mean number of oocytes retrieved was significantly higher in group 2, fertilization rates, miscarriage rates, delivery rates/stimulation cycle, and the incidence of OHSS did not differ significantly between the two groups. CONCLUSION: Withholding gonadotropin administration is an effective alternative to prevent the development of severe OHSS in a high-risk population. Although the risk of cancellation cannot be completely eliminated, this strategy can provide a high pregnancy rate without the need to repeat multiple frozen-thawed cycles.

Aneuploidy 16 in human embryos increases significantly with maternal age.

OBJECTIVE: To determine aneuploidy for chromosome 16 by recycling nuclei of cells already analyzed for chromosomes X, Y, 18, 13, and 21 using multiple fluorescence in situ hybridization in preimplantation human embryos in a time frame compatible with clinical IVF and to asssess the incidence of chromosome 16 aneuploidy in embryos related to maternal age. DESIGN: Prospective experimental study. SETTING: In vitro fertilization program in a tertiary center. PATIENTS: One hundred four consenting patients undergoing IVF. MAIN OUTCOME MEASURES: Chromosome 16 ploidy was analyzed in a total of 195 embryos. In 89 embryos, a standard multiple-probe fluorescence in situ hybridization was used for chromosomes X, Y, 18 and 16 (series 1). The remaining 106 embryos (series 2) were reanalyzed with a new procedure for chromosome 16, which involves rehybridization with a digoxigenin-labeled alpha satellite probe after the standard analysis for chromosomes X, Y, 18, 13, and 21 was completed. The embryos were assigned to one of three groups according to the women's age; group 1: /= 40 years (n = 23). RESULTS: Successful analysis, including biopsy, fixation, and fluorescence in situ hybridization was achieved in 86% of the blastomeres within approximately 10 hours. A significant relationship was found between the rate of aneuploidy for chromosome 16 and increasing maternal age: group 1: 0%, group 2: 6.3%, and group 3: 11.7%. Monosomy for chromosome 16 was found in 72.7% of the 11 embryos carrying chromosome 16 anomalies, with the remaining three embryos having two trisomies and one tetrasomy. This new protocol was applied clinically to five patients undergoing preimplantation aneuploidy assessment. Aneuploidy for chromosome 16 was found in five embryos from three of those patients. CONCLUSIONS: This study demonstrates that preimplantation genetic diagnosis of the major human aneuploidies is achievable within a time frame compatible with IVF. In addition, this study confirms, for embryos, the existing data from spontaneous abortions suggesting that chromosome 16 aneuploidy increases with maternal age. The high prevalence of embryonic monosomy, which is rarely found in spontaneous abortions, suggests that monosomy 16 could be a factor associated with failure of implantation, as well as pointing to a different mechanism involved in the generation of chromosome 16 aneuploidy.

The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities.

The purpose of the present study was to determine whether the presence of one or more multinucleated blastomeres during early embryonic development is associated with chromosomal abnormalities in sibling blastomeres of that embryo. Embryos with multinucleated cells (n = 47) detected on day 2 or 3 or development were compared to dividing embryos without multinucleation. Arrested embryos were excluded from this study. Chromosome abnormalities were detected using fluorescent in-situ hybridization (FISH) with X, Y, 18 and 13/21 chromosome-specific probes. Of 47 embryos included in this study, 76.6% were chromosomally abnormal, compared to 50.9% in the control group (P < 0.001). Excluding aneuploidy, which is originated in the gametes and not the embryo, the differences were even higher, with 74.5% of multinucleated embryos being chromosomally abnormal compared to 32.3% of non-multinucleated embryos (P < 0.001). Day of multinucleation appearance, number of nuclei per cell, number of multinucleated cells per embryo and developmental quality of the embryos as well as the type of fertilization (intracytoplasmic sperm injection versus standard insemination) were not found to affect the rate of chromosomal abnormalities in embryos with multinucleated cells. These results suggest that embryos with multinucleated cells may not be suitable for replacement and should be excluded unless no other embryos are available.

In vitro fertilization versus tubal surgery: is pelvic reconstructive surgery obsolete?

OBJECTIVE: To compare the results of pelvic reconstructive surgery with cumulative success rates of IVF for couples with tubal factor infertility. DATA RESOURCES: Outcomes of pelvic surgery were obtained from a review of articles from the literature identified by directed Medline searches. Cumulative pregnancy rates of 771 couples with tubal factor infertility treated at the Cornell IVF program between December 1989 and December 1992 were calculated by life-table analysis. RESULTS: Overall delivery rate per transfer for patients with tubal factor was 28.9% (303 deliveries per 1,048 transfers) and did not appear to be affected significantly by the presence of a secondary diagnosis. A significant decline in pregnancy rates was observed with advancing age: age < 30 years, 48.4%; 30 to 34 years, 44%; 35 to 38 years, 28%; 39 to 40 years, 20%; 41 to 42 years, 9%; and > 42 years, 4.3%. Cumulative pregnancy rates for cycles 1 to 4 were 32%, 59%, 70%, and 77%, respectively, in patients with only tubal factor, and 28%, 55%, 62%, and 75% in patients with tubal combined with other associated infertility factors. CONCLUSIONS: Our experience suggest that > 70% of women with tubal factor infertility will have a live birth within four cycles of treatment with IVF. These results compare favorably with the best outcomes after tubal reconstructive surgery. In older women, because of the rapid decline of fertility potential with advancing age, efforts should be directed toward the treatment method that provides the highest likelihood of success within the shortest time interval.

Massive deep vein thrombosis in a patient with antithrombin III deficiency undergoing ovarian stimulation for in vitro fertilization.

OBJECTIVE: To present the first report of a thromboembolic complication in early pregnancy after ovarian hyperstimulation for IVF in a patient with AT III deficiency who was treated successfully and subsequently delivered a healthy male infant at 32 weeks of gestation. DESIGN: Case report. SETTING: Hospital-based clinic for reproductive medicine. PATIENT: A 28-year-old woman who consulted our IVF clinic with a 3.5-year history of primary infertility. INTERVENTIONS: Intravenous heparin therapy. RESULTS: The patient responded adequately to heparin therapy and was discharged home on SC heparin. A primary cesarean section was performed at 32 weeks of gestation because of poor fetal growth and transverse lie. CONCLUSIONS: We stress the importance of obtaining a thorough personal and family history before initiation of ovarian hyperstimulation. Measuring activity of AT III, protein C, and protein S in patients with a suspicious history of thromboembolic episodes occurring at an early age may lead to the implementation of appropriate prophylactic measures, preventing potentially life-threatening complications.

Clomiphene citrate and hMG: an alternative stimulation protocol for selected failed in vitro fertilization patients.

PURPOSE: This study was carried out to evaluate the potential role of the combination clomiphene citrate/human menopausal gonadotropin (CC/hMG) for patients who failed previous in vitro fertilization (IVF) attempts with gonadotropin-releasing hormone analogs (GnRH-a) and/or exogenous gonadotropins. METHODS: Patients were stimulated with CC/hMG (n = 93) after unsuccessfully undergoing 182 gonadotropin cycles with (n = 106) or without (n = 76) luteal-phase GnRH-a. Cancellation rate, length of stimulation, and peak estradiol levels did not differ significantly between the two regimens. RESULTS: Although fewer oocytes were retrieved when the CC/hMG combination was used, 16 patients were able to successfully achieve a pregnancy (26.2% delivery rate/transfer). When daily follicle stimulating hormone (FSH) levels were measured in two successive cycles in those women who conceived with the CC/hMG stimulation, baseline levels did not differ when compared with a previous GnRH-a/hMG cycle. Nevertheless, serum FSH levels rose rapidly and remained higher in the GnRH-a/hMG cycle, reaching significantly higher levels on day of human chorionic gonadotropin (hCG) administration. CONCLUSION: Selected patients who failed previous IVF attempts with gonadotropins with or without GnRH analogs may benefit from the addition of CC to their ovarian stimulation protocol.

Management of benign ovarian cystic teratomas: laparoscopy compared with laparotomy.

STUDY OBJECTIVE: To determine the outcomes of laparoscopic management of benign ovarian cystic teratomas (dermoids) compared with traditional laparotomy and excision. DESIGN: A retrospective analysis of patients treated from October 1988 to May 1993. SETTING: University of Connecticut Health Center-affiliated hospitals. PATIENTS: Thirty-eight women with dermoid cysts that were managed either by laparotomy or laparoscopy, 19 matched patients in each group. The majority of lesions in both groups were diagnosed at routine pelvic examination. INTERVENTIONS: The two groups were assessed with respect to age, gravidy, parity, size of lesions, and estimated blood loss at surgery. MEASUREMENTS AND MAIN RESULTS: Two values were significantly different in the group treated by laparoscopy: more dermoids ruptured intraoperatively, and the mean hospital stay was significantly shorter (p

Superovulation with human menopausal gonadotropins is associated with endometrial gland-stroma dyssynchrony.

OBJECTIVE: To investigate the prevalence of endometrial inadequacy in endometrial biopsies from women undergoing superovulation with hMG and to correlate these findings with the hormonal milieu. DESIGN: Controlled, retrospective analysis. SETTING: University-based, tertiary referral, outpatient infertility clinic. SUBJECTS: Endometrial biopsies were performed during the late luteal phase in 89 women undergoing hMG superovulation combined with IUI. Results were compared with the initial biopsies obtained as part of their routine infertility evaluation. MAIN OUTCOME MEASURES: Biopsies were dated by two different observers using standard dating criteria. Serum samples obtained during the midluteal phase were assayed in duplicate for E2 and P levels using commercially available RIAs. RESULTS: Fifty-seven percent of the endometrial biopsies showed differences in the dating of the glandular epithelium that differed by > 2 days when compared with the stroma. In contrast, only 13% of endometrial biopsies obtained during a nonstimulated cycle showed gland-stroma dyssynchrony. When cycles associated with gland-stroma dyssynchrony were compared with cycles associated with coordinated development of the glands and stroma, no significant differences were observed in E2 level on the day of hCG administration, midluteal serum P, midluteal E2 level, or P:E2 ratios. CONCLUSIONS: This study demonstrates that when endometrial biopsies are obtained during the late luteal phase in patients undergoing ovarian hyperstimulation there is a significant dyssynchrony in the maturation of the glandular epithelium and the stroma. This may reflect the degree of responsiveness of an individual woman's endometrium rather than a result of the hormonal milieu.

Comparison of different regimens of a gonadotropin-releasing hormone analog during ovarian stimulation for in vitro fertilization.

Three treatment protocols were used in 156 in vitro fertilization cycles. Leuprolide acetate was begun on day 1 of the cycle in one group (n = 20), on day 3 in another (n = 48), and the third control group (n = 88) did not receive the gonadotropin-releasing hormone analog. Human menopausal gonadotropin was initiated on day 3 in all groups. Peak estradiol (E2) levels and the mean numbers of mature oocytes and embryos transferred per cycle were significantly greater in the day 3 group than in either the day 1 or control groups. Patients who received the day 3 protocol had significantly fewer cancelled cycles. A decline in E2 was observed on the third day of analog administration in certain patients, particularly those on the day 1 protocol. Follicle-stimulating hormone and luteinizing hormone (LH) levels increased two- to fivefold 24 hours after initiation of the analog. Thereafter the gonadotropin levels fell, but nevertheless remained above those of controls for most of the cycle. Hence, it appears that enhanced follicular growth attributed to the early transient rises in gonadotropins can be coupled to a suppression of endogenous LH surges in leuprolide-treated women. These beneficial effects seem to be more likely to occur if leuprolide is initiated on cycle day 3 rather than day 1.

Bovine serum albumin (BSA) can replace patient serum as a protein source in an in vitro fertilization (IVF) program.

Alternate protein sources have been suggested to replace the commonly used cord or patient serum for in vitro fertilization (IVF) procedures. During an 11-month period 127 patients treated for in vitro fertilization had either their serum (N = 71) or bovine serum albumin (BSA; N = 56) used as the protein source in the insemination and growth media. Ham's F-10 + 0.5% BSA was used for sperm swim-up and insemination media and 1% BSA was used for the growth media. Patient's serum was added to Ham's F-10 culture media at concentrations of 7.5 and 15% for insemination and growth, respectively. Embryo transfer was performed with Ham's F-10 containing 90% maternal serum in both groups. Fertilization rate of 259 oocytes inseminated in medium containing patient's serum did not differ when compared with 200 oocytes inseminated in medium containing BSA. Likewise, rates of abnormal fertilization, cleavage, and pregnancy were similar in both groups. In a second experiment, 148 normally fertilized oocytes were transferred after 24 hr in culture to growth media containing two different concentrations of BSA (0.5 or 1%). Cleavage rates for the two groups were similar and the percentage of embryos developed to greater than or equal to 4 cells did not differ significantly. We conclude that a single concentration of BSA can safely be used to supplement culture media in human IVF with several practical and economical benefits.

Cortisol levels in human follicular fluid.

This study shows that cortisol levels in follicular fluids in stimulated cycles were correlated with oocyte maturity and in vitro fertilizability. The levels were significantly higher than the concentrations found in spontaneous cycles. Our findings suggest that the presence of cortisol in follicular fluid may play a role in follicular development and oocyte maturation.

Collagen matrix influences the morphologic features and steroid secretion of human granulosa cells.

Steroid secretion and structure of granulosa cells on floating collagen gels were compared with those of cells grown on plastic. Granulosa cells from follicles of gonadotropin-treated women were plated either onto dishes coated with type I collagen or onto plastic dishes. Medium containing serum was removed after 24 hours, defined medium was added, and the gel was floated. Medium was changed daily for 3 days, after which the granulosa cells were prepared for light and electron microscopy. Cells grown on collagen secreted significantly more estradiol and progesterone than those grown on plastic during the 3 days of culture. The round multilayered granulosa cells on collagen had abundant mitochondria and lipid droplets and they formed numerous intercellular junctions. On plastic surfaces, flat granulosa cells grew as a monolayer with few junctions and less abundant mitochondria or lipid droplets. We conclude that growth on floating collagen promotes structural changes of human granulosa cells that enhances cell interaction and secretion of steroid hormones.

An increased initial follicle-stimulating hormone/luteinizing hormone ratio does not affect ovarian responses and the outcomes of in vitro fertilization.

The tenet that a combination of human follicle-stimulating hormone (hFSH)/human menopausal gonadotropin (hMG) improves follicular recruitment was assessed by randomly treating ovulatory women either with hFSH/hMG on days 3 and 4 of the cycle followed by two ampules of hMG daily or with a constant daily dose of 2 ampules of hMG. Estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) and the mean number of mature, immature and atretic oocytes per cycle did not differ between the two groups. Likewise, fertilization, cleavage, and pregnancy rates were similar for the two treatments. When daily hormone levels were compared in 11 patients during two successive treatment cycles with both stimulation protocols, the temporal pattern of FSH accumulation was repeated in both cycles, but FSH levels were significantly higher when patients received hFSH/hMG. Nevertheless, during both cycles, E2 reached similar peak levels and the mean number of follicles per cycle on the day of hCG administration was not different. We conclude that routine use of hFSH/hMG does not improve the success of an in vitro fertilization (IVF) program and that higher FSH levels do not change the individuality of ovarian response in the same woman.

Ovarian response to human menopausal gonadotropin following suppression with oral contraceptives.

The main conclusion of this study is that a profound suppression of the pituitary and ovary can be associated with an inadequate response which may require a longer or different regimen of stimulation to achieve the desired outcome for IVF. We suggest that a pretreatment determination of E2 and gonadotropins can be of value to predict the nature of ovarian response in women with suppressed pituitary-ovarian function.

PIP: A profound suppression of the pituitary and the ovary is connected to an inadequate response to gonadotropin therapy. The therapy, used to produce multiple follicular development for in vitro fertilization (IVF), can cause a variety of responses including: premature luteinization, inadequate amount of preovulatory follicles and an asynchrony of follicular maturation. The aforementioned responses are related to lowered IVF success. IVF patients who received oral contraceptives as part of treatment had undesirable responses to human menopausal gonadotropin when the contraceptives were administered for only a short period. It is suggested that a different regimen be pursued to achieve adequate responses. A pretreatment determination of E and gonadotropins is a viable method of predicting ovarian response among women who have suppressed pituitary-ovarian function. It is further concluded that a favorable response to hMG was not found in IVF patients when treatments of oral contraceptives are administered for a short period.