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Objective: To study the association between the number of blastocysts available and pregnancy outcomes in first fresh autologous single blastocyst transfer cycles., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): Patients from the Society for Assisted Reproductive Technology reporting fertility clinics (n=16,666)., Interventions(s): None., Main Outcome Measure(s): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of blastocysts and each outcome., Result(s): When comparing fresh single blastocyst transfer rates, the odds of a positive pregnancy outcome (CP) increased significantly with each additional supernumerary blastocyst up to five and declined by 2% for every additional blastocyst after five. Similarly, the odds of an LB was 17% higher for each additional blastocyst up to five and declined by 2% for every additional blastocyst after five. There was no significant association between blastocyst number and miscarriage rate., Conclusion(s): Odds of positive pregnancy outcomes (CP, LB) increased significantly with every additional blastocyst up to five, but declined after that, in first fresh autologous cycles with single-blastocyst transfer. The decline after five may be explained by a detrimental effect on endometrial receptivity in patients with a large number of oocytes or inadequate selection of the best embryo for transfer based on morphology alone., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the association between the total number of fertilized oocytes available and pregnancy outcomes in first fresh IVF cycles with a single blastocyst transfer., Design: Retrospective cohort study., Setting: Not applicable., Patient(s): A total of 15,803 patients from SART reporting fertility clinics., Intervention(s): None., Main Outcome Measure(s): Primary outcomes were clinical pregnancy (CP), live birth (LB), and miscarriage rates. Logistic regression was used to investigate the association between the number of fertilized eggs and each outcome., Result(s): The median number of total oocytes was 15, and the median number of fertilized oocytes was nine. The odds of a clinical pregnancy were 8% higher for each additional fertilized oocyte up to nine (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.07-1.10) and declined by 9% for every additional fertilized oocyte after nine (OR 0.91; 95% CI 0.89-0.94). Similarly, the odds of an LB was 8% higher for every additional fertilized oocyte up to none (OR 1.08; 95% CI 1.06-1.10) and declined by 8% for every additional fertilized oocyte over nine (OR 0.92; 95% CI 0.90-0.94)., Conclusion(s): Odds of pregnancy outcomes (CP, LB) increase significantly with every additional fertilized oocyte up to nine, and CP and LB decline after that in first fresh autologous cycles with a single blastocyst transfer., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Ovarian endometriomas are a common manifestation of endometriosis that can represent a more severe stage of the disease. There is much debate over the treatment of these cysts in infertile women, particularly before use of assisted reproductive technologies. Evidence exists that supports surgical excision of ovarian endometriomas, as well as evidence that cautions against surgical intervention. Certain factors need to be examined closely before proceeding with surgery or continuing with expectant management. These include the patient's symptoms, age, ovarian reserve, size and laterality of the cyst, prior surgical treatment, and level of suspicion for malignancy. The most recent evidence appears to suggest that certain patient profiles may benefit from proceeding directly to in vitro fertilization (IVF). These include symptomatic infertile patients, especially those that are older, those that have diminished ovarian reserve, those that have bilateral endometriomas, or those that have had prior surgical treatment. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman's ovarian reserve. Nevertheless, the presence of an endometrioma does not appear to adversely affect IVF outcomes, and surgical excision of endometriomas does not appear to improve IVF outcomes. Regardless of treatment plan, infertile patients with endometriomas must be counseled appropriately before choosing either treatment path.

Women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility were randomly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH (r-hFSH; Gonal-F) and recombinant human LH (r-hLH; Luveris) (n = 212) starting on day 6 of FSH stimulation until human chorionic gonadotrophin (HCG) at a daily fixed dose of 150 IU r-hLH, or with r-hFSH alone (n = 219). There was no significant difference in the number of metaphase II oocytes retrieved (10.3 versus 10.4) in patients treated with r-hFSH and r-hLH versus r-hFSH alone; however, more embryos were transferred in the LH-supplemented group (2.9 versus 2.8, P = 0.037). Overall, the implantation rates were 22.9 versus 27.0% in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively (NS). The respective numbers of MII oocytes retrieved in patients <35 or >or=35 years were 11 versus 8.3 (P = 0.010) for patients treated with r-hFSH alone, and 10.7 versus 9.3 (NS) for those given supplemental r-hLH (150 IU) from day 6. Implantation rates in patients <35 years treated with r-hFSH were higher (30.7%) than those receiving r-hFSH and r-hLH, (23.5%) (P = 0.068). In patients >or=35 years, the implantation rates were 21.7% for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7% when treated with FSH alone (NS). Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol, but women >or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH.

Objective: To compare IVF outcome between two protocols for luteal phase supplementation, one beginning on day 3 after oocyte retrieval and the other beginning on day 6 after retrieval., Design: Prospective, randomized study., Setting: University-based assisted reproductive technology center., Patient(s): One hundred twenty-six consecutive patients undergoing IVF between January and July 2000., Intervention(s): Patients were randomized to begin luteal phase support using vaginal progesterone beginning either on day 3 after oocyte retrieval or on day 6 after oocyte retrieval., Main Outcome Measure(s): Clinical pregnancy rates and implantation rates., Result(s): All patients randomized underwent transfer. There were no differences in age, oocytes retrieved, or embryos transferred between the two groups. Those patients receiving luteal phase support with progesterone beginning on day 6 after retrieval had a significantly lower clinical pregnancy rate per transfer compared with those beginning support on day 3 after retrieval (44.8% vs. 61.0%, respectively). This difference in pregnancy rates was greater in those patients undergoing a luteal gonadotropin releasing hormone (GnRH) agonist down-regulation protocol (47.5% vs. 71.4%, day 6 vs. day 3, respectively). Beginning support on day 6 also significantly decreased implantation rates in the GnRH agonist group (21.0% vs. 34.0%, day 6 vs. day 3, respectively)., Conclusion(s): Pregnancy rates are significantly decreased by initiating luteal-phase progesterone supplementation on day 6 after oocyte retrieval during in vitro fertilization cycles.

Purpose: To examine the impact of low basal cycle day 3 serum LH levels or a high FSH:LH ratio on IVF results., Methods: A homogeneous group of patients was analyzed as identified by normal basal cycle of follicle stimulating hormone (FSH), Luteinizing hormone (LH), and estradiol (E2) levels. High responders (high LH:FSH ratio) and low responders (high FSH or E2 levels, and women > or = 42 years of age) were excluded from analysis. Only cycles stimulated with a combination of a GnRHa (luteal suppression) and pure FSH were studied., Results: Patients with low basal LH levels (< 3 mIU/mL) did not differ significantly from controls in terms of response to controlled ovarian hyperstimulation but there was a clear trend toward poorer implantation and clinical pregnancy rates. On the other hand, patients with a high FSH:LH ratio (> 3) had significantly fewer mature oocytes aspirated, and lower implantation and clinical pregnancy rates than patients with gonadotropin ratio < or = 3. These negative effects were evident in the presence of normal basal FSH levels and after adequate matching of female's age and number of embryos transferred., Conclusions: These studies highlight a negative impact of a basal cycle high FSH:LH ratio (and possibly low LH levels) on follicular development and oocyte quality in these patients subjected to pituitary down-regulation followed by pure FSH administration. A high FSH:LH ratio may be therefore used as an early biomarker of poor ovarian response.

Objectives: To analyze the outcome of intracytoplasmic sperm injection (ICSI) cycles in infertile couples in whom the main diagnosis of infertility was azoospermia of obstructive and nonobstructive origin., Methods: Eighty-three consecutive ICSI cycles were carried out with retrieved testicular or epididymal spermatozoa, 60 cycles in 32 patients with obstructive azoospermia and 23 cycles in 12 patients with nonobstructive azoospermia. Fifty-four testicular biopsies (testicular sperm extraction) and 18 epididymal aspirations (microepididymal sperm aspiration) were performed.Results. Motile spermatozoa were recovered in 65 cycles (90.3%). In another 3 (4.2%), nonmotile spermatozoa were retrieved. In 4 patients (5.5%), sperm could not be recovered. In 11 cycles, frozen sperm from a previous procedure were used. A significantly lower fertilization rate (64% versus 73%, P = 0.02), clinical pregnancy rate (13% versus 47%, P <0.001), and good embryo quality rates (35% versus 56%, P = 0.009) were observed in patients with nonobstructive azoospermia. In patients with obstructive azoospermia, no significant differences were observed when the outcome was analyzed on the basis of the sperm origin (ie, from testicular sperm extraction or microepididymal sperm aspiration)., Conclusions: When combining testicular sperm extraction or microepididymal sperm aspiration with ICSI in patients with obstructive azoospermia, the results in terms of fertilization, implantation, and pregnancy rates were similar to those found in patients with nonazoospermic obstruction who underwent ICSI with ejaculated sperm. Patients with nonobstructive azoospermia had lower fertilization, embryo quality, and pregnancy rates than did those with obstructive azoospermia, probably because of severe defects in spermatogenesis, leading to poor gamete quality. The urologist and reproductive endocrinologist now have an excellent therapeutic option to offer men with previously intractable infertility.

Objective: To investigate the use of donated gametes for the production of human embryonic stem cell lines., Design: Basic research study., Setting: Assisted Reproductive Technology (ART) program at an academic institution., Patient(s): Consenting oocyte and sperm donors., Intervention(s): None., Main Outcome Measure(s): Oocytes were aspirated from oocyte donors (n = 12) and inseminated with frozen-thawed donor (n = 2) sperm followed by culture of embryos to day 5 or 6 in sequential media. The inner cell masses of expanded blastocysts were isolated using immunosurgery and cultured for 4-11 days on irradiated primary mouse embryonic fibroblasts (PMEFs). Viable cell colonies were passed every 7-10 days onto fresh PMEFs in the presence of leukemia inhibitory factor (0.1 microg/mL) and evaluated for appropriate cell surface markers., Result(s): Immunosurgery of 40 blastocysts resulted in the culture of 18 inner cell masses, which have produced three cell lines. One of these cell lines has been shown to stain positive for alkaline phosphatase and stage-specific embryonic antigen (SSEA)-4 and negative for SSEA-1, express telomerase activity, and produce hCG when allowed to differentiate., Conclusion(s): These findings demonstrate that the future production of human embryonic stem cell lines for therapeutic use is possible with the use of donated gametes. Many ethical issues were considered before the initiation of this study, and it was our goal to ensure that both oocyte and sperm donors understood the nature and purpose of the research before their participating in the study.

Objective: To determine the impact of a cryopreservation program on pregnancy rates and multiple-pregnancy rates in ART cycles., Design: Retrospective study., Setting: University teaching hospital., Patient(s): Women who underwent stimulation for in vitro fertilization at the Jones Institute for Reproductive Medicine between October 1987 and June 1999., Intervention(s): Analysis of pregnancy and multiple-pregnancy rates based on the number of embryos transferred., Main Outcome Measure(s): Implantation; pregnancy and multiple-pregnancy rates., Result(s): Pregnancy rates per transfer increased from 9% when one embryo was transferred to 20% with two embryos, 35% with three embryos, 40% with four embryos, and 41% with five embryos. The rate of twin pregnancies increased to 21% with two embryos, 23% with three embryos, 21% with four embryos, and 22% with five embryos. The triplet pregnancy rates were 8% with three embryos, 9% with four embryos, and 2% with five embryos. A theoretical model limiting the number of embryos transferred to two with cryopreservation and subsequent transfer yields a cumulative pregnancy rate of 77%, a twin rate of less than 20%, and no triplet or higher-order pregnancies., Conclusion(s): The use of a cryopreservation program can help maximize pregnancy rates while minimizing multiple-pregnancy rates. Cryopreservation should be considered in all assisted reproductive technology cycles.

Objective: To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH)., Design: Phase III, multicenter, open-label randomized trial., Setting: In vitro fertilization (IVF) centers in North America., Patient(s): Healthy female partners (n = 313) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated., Intervention(s): Patients were randomized to receive one COH cycle with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection., Outcome Measure(s): Number of oocytes retrieved, pregnancy rates, endocrine variables, and safety variables., Result(s): The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62.4% and 61.9% in the ganirelix and leuprolide groups, respectively, and implantation rates were 21.1% and 26.1%. Clinical and ongoing pregnancy rates per attempt were 35.4% and 30.8% in the ganirelix group and 38.4% and 36.4% in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11.9% and 0.6%) than with leuprolide (24.4% and 1.1%)., Conclusion(s): Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.

To fully evaluate the advantages of a cryopreservation program a method needs to be established to express the additional patients pregnant from cryopreservation. The patient specific method considers cryopreservation as augmentation only among patients without a pregnancy from the fresh transfer, or from previously transferred frozen material from the same harvest. In an analysis of the pregnancy rate at the Jones Institute between January 1996 and December 1998 we found a fresh pregnancy rate of 40.8% in the good responders and 28.8% in poor responders. The patient specific pregnancy rate in the same cycles was 53.4% in good responders and 32.3% in poor responders. Good responders less than 35 years of age with ten or more mature eggs at retrieval had a fresh pregnancy rate of 40.2% and a patient specific pregnancy rate of 57.9%. It is exceedingly important for the physician and patient to understand and comprehend the potential in cryopreserved material.

In our program's 13 years of experience, more than 9000 embryos have been cryopreserved in gonadotropin-stimulated IVF cycles. Over 1500 thaw and transfer cycles have yielded a pregnancy rate of approximately 25%. Different ovarian stimulation regimens (various preparations of FSH. alone or in combination with hMG, with or without concomitant use of a GnRH agonist) did not influence embryo survival or pregnancy rate. Likewise, the application of oocyte/embryo micromanipulation techniques for assisted fertilization (ICSI for male infertility) or assisted hatching (performed selectively) did not have an impact on pregnancy results. Survival and transfer rates of embryos cryopreserved at pronuclear or cleaving stage did not differ significantly. However, implantation and pregnancy rates were higher with pronuclear embryo freezing (day-2 transfers) when compared to embryos frozen at the cleavage stage (day-3 transfers). This may be the result of patient selection and transfer policies. Similar implantation and pregnancy results were achieved in natural and estrogen progesterone supplemented transfer cycles. Initial experience with pronuclear freezing followed by transfer at the blastocyst stage appears to offer a very successful alternative for selected patients.

Purpose: To determine whether embryos resulting from oocytes matured in vitro have a higher incidence of nuclear and/or genetic abnormalities compared to embryos resulting from oocytes matured in vivo., Methods: Fluorescence in situ hybridization analysis for chromosomes X, Y, and 18 was used to compare the rates of aneuploidy, mosaicism, and nuclear abnormalities in embryos derived from oocytes that were prophase I at aspiration (immature group) to that observed in embryos resulting from oocytes that were metaphase I or II at aspiration (mature group)., Results: Based on nuclear morphology, significantly more embryos in the mature group (23%) were classified as normal compared to embryos in the immature group (3%). No difference was found in the rate of aneuploidy or in the incidence of mosaicism involving these chromosomes., Conclusions: These findings suggest that few embryos derived from prophase I oocytes collected following ovarian stimulation are morphologically normal.

Purpose: Our purpose was to examine the timing of implantation and early embryo development following uterine transfer of oocytes/embryos previously subjected to zona pellucida micromanipulation., Methods: A total of 68 singleton pregnancies resulting from IVF and embryo transfer with/without micromanipulation. Patients were divided into four groups according to the type of micromanipulation technique: assisted hatching, embryo biopsy, intracytoplasmic sperm injection, and no micromanipulation (control group). Serial serum beta-hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG10) to estimate detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG, an indirect sign of embryo development., Results: There were no significant differences among groups with respect to hCG10, the slopes or intercepts of the regression lines., Conclusions: Various oocyte/embryo microsurgical procedures used in ART involving zona pellucida manipulation do not appear to affect the timing of implantation or early embryo development.

Objective: The aims of this study were to compare preimplantation embryo quality in intracytoplasmic sperm injection (ICSI) with standard IVF and to examine the impact of age and number and quality of embryos transferred on implantation and pregnancy., Design: Retrospective, controlled clinical study., Setting: Academic tertiary center., Patient(s): We examined 211 consecutive couples undergoing ICSI who were matched with 211 couples undergoing IVF therapy during the same time frame., Intervention(s): In vitro embryo culture., Main Outcome Measure(s): Day 3 embryo quality as judged by the number of blastomeres and morphology scoring., Result(s): Patients undergoing ICSI had a significantly reduced number of embryos with good morphology and cleavage compared with IVF cases. Nevertheless, pregnancy and abortion rates were similar when adjusted by age and number of embryos transferred. Average cleavage status and age were significant predictors of implantation. Women of advanced age had significantly lower embryo cleavage and implantation rates., Conclusion(s): [1] The cleaving status of day 3 embryos is a valuable, although limited, indicator of implantation outcome. [2] In vitro fertilization-derived embryos had better cleavage rates and morphology scores than ICSI-derived embryos; however, the implantation potential was similar for both groups. [3] The age-related decline in implantation rate was associated with impaired embryo growth rates.

The value of gonadotrophin and oestradiol concentrations following pituitary down-regulation with leuprolide acetate in predicting ovarian response to stimulation was evaluated in three groups of women undergoing ovarian stimulation for in-vitro fertilization with highly purified follicle stimulating hormone (FSH). Leuprolide acetate was started in the midluteal phase, and either stopped at menses (IVF-SL group, n = 3), or continued throughout stimulation (IVF-LL group, n = 38; oocyte donors, n = 58). Ovarian stimulation was started on cycle day 3, after blood was drawn for down-regulated FSH, luteinizing hormone (LH) and oestradiol. Higher down-regulated LH was predictive of higher oestradiol on day 5 of stimulation in both IVF groups, and of need for fewer ampoules in the IVF-LL group, but not of oestradiol on day of human chorionic gonadotrophin (HCG) administration or number of oocytes retrieved. Higher FSH after down-regulation predicted yield of fewer oocytes in the donor and IVF-LL groups, and higher oestradiol on day 5 of stimulation, need for fewer ampoules and a shorter duration of therapy in both IVF groups. Higher oestradiol after down-regulation was associated with higher oestradiol on day 5 of stimulation and on day of HCG administration, a shorter duration of therapy and need for fewer ampoules in all groups. Whereas these results do not ascribe any predictive significance to LH, they suggest that oestradiol and FSH concentrations after down-regulation are predictive of the pattern of ovarian response to stimulation and of oocyte yield.

Objective: To determine if frozen-thawed donor oocytes could be used to provide cytoplasm for transfer into patients' oocytes to improve subsequent embryonic development., Design: Prospective evaluation of the procedure in consenting IVF patients., Setting: Assisted reproductive technology program., Patient(s): The study was open to consenting IVF patients (of any age) with a history of poor embryo quality or those couples in which the wife's age was > or = 40 years., Intervention(s): Transfer of donor egg cytoplasm from frozen-thawed oocytes into the oocytes of infertile recipients., Main Outcome Measure(s): Donor oocyte survival following cryopreservation, fertilization following cytoplasmic transfer into recipient oocytes, embryo quality, and pregnancy outcome., Result(s): Oocytes collected from four donors were cryopreserved and 61% (28/46) survived the thaw procedure. Cytoplasmic transfer was performed on the eggs of four patients, with fertilization occurring in 70.3% (26/37). Twin pregnancy was established in one patient (35 years of age) with a history of poor embryo quality., Conclusion(s): Cryopreserved donor oocytes may provide a source of cytoplasm for transfer into recipient oocytes, eliminating the need for cycle synchronization between donor and infertile patient.

Purpose: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels., Methods: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG10), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG., Results: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups., Conclusions: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the healthy, successfully implanted conceptus.

The objective of this study was to investigate the role of the spermatozoon (paternal effects) on implantation and pregnancy outcome in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Male individuals of three types were analysed: infertile men with oligoasthenoteratozoospermia (OAT), infertile men with normozoospermia and fertile men (donors). Female counterparts were judged to have comparable egg quality within two groups studied, i.e. infertile women with pure mechanical (tubal) infertility and recipients of donor eggs. There were significantly higher differences in implantation and pregnancy rates in groups using donor spermatozoa and donor egg recipients. Analyses of key set groups revealed a trend toward a poorer implantation and pregnancy outcome when comparing OAT versus normozoospermic patients within IVF, but not within ICSI treatments, in couples with tubal infertility. In couples who were recipients of donor eggs, no differences were observed between OAT patients treated by ICSI and normozoospermic patients treated with IVF. No significant differences were observed in miscarriage rates within any groups studied. In conclusion, the poorer results observed in OAT patients undergoing IVF may be secondary to spermatozoal effects due to a high insemination concentration. Overall, there does not seem to be a significant effect of severe male infertility (OAT) on implantation and pregnancy outcome. However, this does not preclude that specific sperm aberrations may exert a negative effect on embryogenesis and therefore on implantation potential following assisted or in-vivo reproduction.

Objective: To evaluate the pregnancy results of an ovarian hyperstimulation protocol for IVF-ET that combines GnRH agonist down-regulation, cessation of GnRH agonist therapy with the onset of menstruation, and high-dose gonadotropin administration in low responders., Design: Prospective analysis., Setting: Academic IVF program., Patient(s): One hundred eighty-two low responders undergoing 224 IVF-ET cycles., Intervention(s): Down-regulation was obtained with the administration of leuprolide acetate beginning in the midluteal phase and ending with the onset of menses. Daily administration of 6 ampules of FSH alone or in combination with hMG was initiated on cycle day 3., Main Outcome Measure(s): Stimulation characteristics and pregnancy rates (PRs) were compared between fresh cycles in which pure FSH alone was used and 35 cycles in which a combination of FSH and hMG was administered., Result(s): The clinical PR per transfer, the ongoing PR per transfer, and the implantation rate were 32%, 24%, and 9%, respectively. No differences were noted between cycles in which pure FSH alone was used in comparison with cycles in which a combination of FSH and hMG was administered., Conclusion(s): Short-term ovarian suppression begun in the luteal phase and discontinued with the onset of menses followed by high-dose stimulation with gonadotropins yields favorable pregnancy results in low responders.

The objective of this study was to investigate the impact of severe oligoasthenoteratozoospermia (OAT) on pregnancy outcome. For this purpose 279 consecutive intracytoplasmic sperm injection (i.c.s.i) cycles were retrospectively evaluated and compared to 436 consecutive IVF cycles performed during the same time frame. Group A (n = 62) included ICSI patients with severe OAT; group B (n = 217) included patients who underwent ICSI for other indications; and group C (n = 436) included couples who underwent standard IVF. The mean age of female patients and mean number of embryos transferred were comparable in all groups. No difference was observed regarding implantation, clinical pregnancy, delivery and miscarriage rates between all three groups, but fertilization rate was significantly lower in group A than in groups B and C. It is concluded that couples undergoing ICSI with severe male infertility (OAT) have a slightly reduced fertilization rate but their chances of delivery and pregnancy loss are similar to those of other patients undergoing clinical ICSI and IVF with non-male infertility.

Objective: To review the effects of hydrosalpinx on IVF/ET and the role of salpingectomy., Design: The literature on hydrosalpinx, IVF/ET, embryotoxicity, and salpingectomy for hydrosalpinx was identified through MEDLINE searches and reviewed., Result(s): Hydrosalpinx has been associated with poor fertility prognosis. IVF/ET is a better alternative to tubal surgery for those patients with severe distal tubal disease, and it is also more cost effective. However, the presence of hydrosalpinx has a negative effect on IVF/ET by decreasing the pregnancy rates and implantation rates compared with patients undergoing IVF/ET for tubal disease but without hydrosalpinx. The hydrosalpingeal fluid has been demonstrated to be embryotoxic to developing embryos, thus leading to increased early pregnancy losses. Poor endometrial receptivity has also been demonstrated in the presence of hydrosalpinges. Removal of the hydrosalpinges leads to improved IVF/ET rates comparable to those patients without hydrosalpinx. Therefore, salpingectomy has been recommended for patients with hydrosalpinx who will be undergoing IVF/ET., Conclusion(s): The presence of hydrosalpinx has a negative effect on IVF/ET because of the suspected embryotoxicity of the hydrosalpingeal fluid. Surgical removal of the hydrosalpinx has been shown to improve IVF/ET rates.

The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied.

Purpose: The objectives of this study were (1) to investigate intracytoplasmic sperm injection (ICSI) outcome according to its indications, i.e., a history of failed or poor fertilization and unsuitable sperm parameters for conventional IVF, and (2) to examine the impact of a female's age, sperm concentration, motility, morphology, presence of antisperm antibodies, and hemizona assay (HZA) results on overall outcome., Methods: Two hundred seventy-nine ICSI cycles performed in 207 couples were retrospectively evaluated., Results: Clinical pregnancy and delivery rates were 36.8 and 29.8% for patients with prior failed fertilization, 23.2 and 17.8% for patients who had prior poor fertilization, and 28.6 and 21.3% for patients with unsuitable sperm parameters. The differences among all groups were found to be insignificant. There was a significant, negative correlation between a female's age and pregnancy results. No difference was found in the three basic sperm parameters between those patients who produced and those who did not produce a pregnancy, but the fertilization rate was significantly higher in patients with more adequate sperm parameters. Although there was a trend toward a better fertilization rate in patients with a hemizona index (HZI) greater than 30 (indicative of a superior sperm-zona pellucida binding capacity) than in those with a HZI less than 30, the difference was not significant. There were no differences in fertilization rate according to the presence or absence of antisperm antibodies., Conclusions: Fertilization history in a conventional IVF cycle has no effect on success rates following ICSI, and there is no correlation among the basic sperm parameters, the presence of antisperm antibodies, and pregnancy rates.

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.

Objective: To investigate the effect of donor's age and her prior fertility on recipient pregnancy outcome in our donor egg program., Design: Retrospective cohort analysis., Setting: Large academic infertility center., Patient(s): A total of 568 fresh ETs were analyzed for the effect of the egg donor's age on pregnancy outcome; a subset of these (n = 185) were analyzed for the effect of the egg donor's prior fertility on pregnancy outcome., Intervention(s): Donors were paired with recipients independent of recipient's age and donor's prior fertility status., Main Outcome Measure(s): Recipient clinical pregnancy rates (PRs) and delivery rates for different donor age groups and for nulligravid donors versus donors with proven fertility., Result(s): Donors > or = 33 years old were less likely than younger donors to produce clinical pregnancies and deliveries in their recipients (43.5% versus 26.6% and 35.1% versus 22.1%, respectively). However, there was no difference in clinical PRs or delivery rates between nulligravid donors and donors with proven fertility., Conclusion(s): Donors > or = 33 years of age could be excluded from egg donation because of the lower pregnancy potential of their eggs. However, lack of proven fertility in a donor seems to have no negative impact on pregnancy potential.

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.

We have analysed the use of a programmed cycle of administration of exogenous steroids without prior suppression with a gonadotrophin-releasing hormone agonist (GnRHa) for the transfer of cryopreserved-thawed pre-embryos. From July 1992 to June 1994, 199 cycles (162 patients) were studied. Pre-embryos had been previously cryopreserved at the pronuclear stage using 1.5 M 1,2-propanediol as a cryoprotectant. Preparation of the endometrium was achieved in a step-up regime with transdermal oestradiol patches (0.1 to 0.4 mg). Progesterone in oil (50 mg i.m.) was started on cycle day 13. Pre-embryos were thawed on day 14 and transferred on day 15 after evidence of survival and cleavage. The mean (+/- SD) age of patients undergoing transfer was 35.4 +/- 4.3 years. The mean number of pre-embryos thawed was 4.7 +/- 1.8 with a mean of 3.3 +/- 1.4 pre-embryos being transferred. Eight of the cycles demonstrated follicular development >16 mm prior to thaw and transfer; however, these patients did not demonstrate a luteinizing hormone surge. Mean endometrial thickness on day 13 was 10.8 +/- 2.1 mm. Overall pregnancy rate was 29.2% (57/195). The ongoing or delivery rate was 16.1% (32/195). The rate of preclinical losses per transfer was 6.2% (12/195). Overall, the implantation rate was 6.2% (47/757). Thus, the use of a programmed cycle for cryopreserved embryo transfer yields favourable pregnancy outcome and offers practical advantages to patients. Prior suppression with a GnRHa is not necessary for endometrial preparation.

Purpose: In the human, intracytoplasmic sperm injection is typically performed using "viable" sperm which has been mechanically rendered nonmotile. The purpose of the present study was to determine the ability of nonviable sperm to fertilize human oocytes and the early developmental normalcy of the resulting embryos., Methods: In this study, immature, prophase I oocytes from a total of 27 consenting patients were matured in vitro and then randomized into two groups: injection with a viable human sperm or injection with a sperm rendered nonviable by freeze-thawing in liquid nitrogen. The rates of fertilization and cleavage were compared between the two groups., Results: The results demonstrated a significantly higher two-pronuclear fertilization rate when oocytes were injected with viable sperm (62.2%) compared to when oocytes were injected with nonviable sperm (16.2%). Oocytes injected with viable sperm also demonstrated a higher cleavage rate (91 vs 33%)., Conclusions: These findings suggest that while the intracytoplasmic injection of nonviable human sperm can result in normal fertilization, it does so at a much reduced rate compared to viable sperm and may not result in normally cleaving embryos.

Objective: To analyze the differences in pregnancy rates (PRs) from the transfer of fresh and cryopreserved embryos from the same cohort of oocytes based on serum P levels on the day of hCG administration and the day after., Design: Retrospective analysis., Setting: Infertility patients stimulated for IVF-ET in an academic center., Patient(s): Three hundred thirty-three patients with fresh transfer and at least one transfer of cryopreserved embryos from the same cohort of recruited oocytes. All stimulations were down-regulated with a GnRH agonist in a long protocol before gonadotropin stimulation., Main Outcome Measure(s): Clinical PR., Result(s): The clinical PR in fresh cycles was 24% for the P < or = 0.9 ng/mL group (group A; conversion factor to SI unit, 3.18) and 34% for the P > 0.9 ng/mL group (group B). Group B patients were younger, received fewer ampules of gonadotropins, had higher peak E2 levels, and had more mature oocytes. There were no significant differences in the P levels on the day of hCG between patients who conceived in both fresh and cryopreserved cycles and any other combination of pregnancy outcome sequence., Conclusion(s): These findings suggest that serum P level cutoffs, on the day of hCG and the day after, as a means of making clinical decisions with respect to cancelling the fresh transfer and cryopreservation of all embryos for future transfer should be questioned.

The objective of this study was to assess fertilization, implantation and pregnancy rates in infertile patients with severe teratozoospermia [P (poor prognosis) pattern sperm morphology assessed by strict criteria] treated by in-vitro fertilization (IVF) using a high insemination concentration (HIC), or by intracytoplasmic sperm injection (ICSI). This was a retrospective cohort study performed in an academic tertiary institution. The outcome of 115 consecutive ICSI cycles was compared to that of a similar number of cycles of IVF with HIC performed during a similar time frame and matched by woman's age and basal serum (cycle day 3) follicle stimulating hormone concentrations. The inclusion criteria were sperm morphology /=1x10(6) total motile spermatozoa per ejaculate. The diploid fertilization rate in the HIC-IVF group was 86% and in the ICSI group 68% (P < 0.05). Importantly, an equal number of embryos was transferred to both groups of patients. The morphological quality of the embryos (proportion of transfers having superior morphology embryo scores) was significantly better in the ICSI group than in the patients receiving HIC-IVF. Although there was a clear trend for better implantation and pregnancy rates in the ICSI group, these differences were not statistically significant. We conclude that, although HIC-IVF resulted in a higher fertilization rate than ICSI in patients with severe teratozoospermia, ICSI produced a significantly higher proportion of morphologically superior embryos with a tendency towards a higher implantation potential. Therefore, teratozoospermic patients having adequate numbers of motile spermatozoa should be offered ICSI as an alternative to modified (HIC) IVF treatment.

Objective: To evaluate the suppression and flare regimens of gonadotropin-releasing hormone agonist (GnRH-a) in ovarian hyperstimulation in women with variable basal gonadotropin values in an in vitro fertilization (IVF) program., Study Design: A retrospective study comparing the initiation of GnRH-a in the midluteal phase of the preceding cycle (suppression protocol) and follicular phase of the stimulated cycle (flare protocol) in women with basal follicle-stimulating hormone (FSH) values < 15 mIU/mL and > or = 15 mIU/mL., Results: The pregnancy rate per initiated cycle and implantation rate for women with basal FSH levels > or = 15 mIU/mL were 20.4% and 9.8% in flare GnRH-a cycles and 11.7% and 3.5%, respectively, in suppression GnRH-a cycles. Comparing the percent differences in clinical pregnancy and implantation rates between both protocols for women with different basal FSH values, pregnancy outcome was significantly greater in the flare protocols in women with values > or = 15 mIU/mL (P < .001). Individualization of the stimulation protocol by retrospective sorting of women undergoing IVF with respect to their basal gonadotropin levels significantly improved clinical pregnancy (P < .05) and implantation rates (P < .05) and reduced the cancellation rate (P < .05)., Conclusion: The flare regimen with GnRH-a is a useful alternative for controlled ovarian hyperstimulation in women with elevated basal FSH values (> or = 15 mIU/mL) undergoing IVF.

Objective: To determine if the incidence of multiple gestations after IVF differs significantly depending on the number of embryos transferred and maternal age., Design: Retrospective analysis of IVF database., Setting: Tertiary care academic center., Patients: One thousand eight hundred sixty-seven patients undergoing IVF with up to four embryos transferred during 1986 through 1993., Main Outcome Measures: The rate of singleton and multiple gestations > 20 weeks estimated gestational age (EGA)., Results: The incidence of triplet gestations > 20 weeks EGA among patients < or = 34 years of age with three versus four embryos transferred was 0.3% (1/335) versus 2.4% (15/662), respectively. The incidence of twin gestations > 20 weeks EGA among patients < or = 34 years of age with two versus four embryos transferred was 1.3% (3/234) versus 7.4% (46/622), respectively. Also among patients < or = 34 years of age, the incidence of singleton gestations > 20 weeks EGA with two versus three embryos transferred was 12.8% (30/234) versus 15.8% (53/335); with two versus four embryos was 12.8% (30/234) versus 17.2% (107/622); and with three versus four embryos was 15.8% (53/335) versus 17.2% (107/622), respectively., Conclusions: In women < or = 34 years of age undergoing IVF-ET, the transfer of four versus three and four versus two embryos significantly increased the incidence of triplet and twin gestations, respectively, without significantly improving the chance of singleton conception. This implies that a policy of transferring only three embryos should be considered in this age group (realizing that such a policy may merit modulation if pretransfer embryo selection is used.).

The objective of this study was to assess the impact on pregnancy outcome of excising hydrosalpinx(ges) in patients with repeated in-vitro fertilization (IVF) failures. A group of 15 patients who had previously undergone failed IVF attempts and had unilateral or bilateral hydrosalpinx was subjected to an operative laparoscopy with excision of the affected tube(s). Of these, 10 patients underwent a unilateral salpingectomy and five had a bilateral salpingectomy. Stimulated cycles of IVF and/or cryo-thaw cycles were then carried out post-salpingectomy and the results were compared to those of pre-salpingectomy cycles. There was no statistically significant difference between the number of mature eggs retrieved, peak oestradiol concentrations, number of days to human chorionic gonadotrophin administration, or number of pre-zygotes frozen in the stimulated cycles pre- versus post-salpingectomy. Pre-salpingectomy, 15 patients underwent 38 stimulated cycles and eight patients underwent 14 cycles with cryopreserved-thawed embryos, achieving one pregnancy from a fresh transfer that resulted in a miscarriage. Post-salpingectomy, eight patients underwent 12 stimulated cycles, achieving five clinical pregnancies (two miscarriages and three ongoing pregnancies, i.e. either delivered or a pregnancy > or = 20 weeks), and nine patients underwent 10 cycles with cryopreserved-thawed embryos, achieving four clinical pregnancies (one miscarriage and three ongoing). We conclude that excision of hydrosalpinx(ges) improves the pregnancy potential after IVF, and that new and repeat IVF patients should be counselled accordingly.

Objective: To determine the efficacy and factors affecting outcome of intracytoplasmic sperm injection (ICSI) in patients with severe male factor infertility., Design: Prospectively designed clinical trial of patients selected to participate in the study based upon the following inclusion criteria: previous total failed fertilization or unsuitable sperm parameters for conventional IVF., Setting: Tertiary care academic center., Patients: Ninety-two consecutive couples undergoing IVF therapy augmented with ICSI during April through December 1994 were studied., Main Outcome Measures: Fertilization and ongoing implantation and pregnancy rates (PRs)., Results: A total of 1,163 preovulatory oocytes were manipulated, yielding a diploid fertilization rate of 60.9%; the oocyte damage rate was 13.2%. The transfer rate was 95% with 43.1% of cycles having excess embryos that were cryopreserved. Overall, the clinical and ongoing PRs per transfer were 31.9% and 26.8%, respectively. None of the sperm parameters of the original semen analysis correlated with ICSI outcome. Female age did not affect fertilization results but had a significant impact on PR (< 34 years: 48.9%; 35 to 39 years: 22.9%; > or = 40 years: 5.9% clinical PR per transfer)., Conclusions: Intracytoplasmic sperm injection offers a new and powerful therapeutic option to treat couples with severe male factor infertility associated with a variety of sperm abnormalities. An adequate female age is a pivotal factor determining a successful outcome.

A simple evaluatory formula for reporting pregnancy rates involving cryopreserved material has so far remained elusive. It is highly desirable to have a method which would allow not only an evaluation of cryotechnology per se, but also an evaluation of the role of cryotechnology in enhancing the total reproductive potential of a single cycle. In this paper, nine separate formulae are described which can be used for the evaluation of cryopreservation. It is concluded that none of the existing formulae used alone expresses the total potential of cryopreservation, and that while each formula provides information regarding some aspect of the role of cryopreservation, the most comprehensive evaluation requires the answer to five different equations. The other four formulae, while often used, are regarded as providing information which is unsubstantiated or does not allow complete evaluation.

The present study was conducted to determine if the cryopreservation of immature human oocytes has a deleterious effect on the meiotic spindle following maturation in vitro. Oocytes were obtained in excess from in-vitro fertilization patients and divided into four groups. Groups 1 (n = 98) and 2 (n = 80) consisted of immature oocytes cryopreserved before or after maturation in vitro respectively. Groups 3 (n = 37) and 4 (n = 9) served as non-frozen controls and included oocytes matured in vitro and in vivo respectively. The meiotic spindle was identified after incubation in anti-tubulin monoclonal antibody (1 h, 37 degrees C) and fluorescein-conjugated goat anti-mouse immunoglobulin G (IgG) (1 h, RT). Chromosomes were counterstained with 4',6'-diamidino-2-phenylindole. Following cryopreservation, group 1 oocytes demonstrated a 63% survival rate and 68% maturation rate in vitro. In all, 58% of the oocytes in group 2 survived the thaw. The number of oocytes with normal spindles in group 1 (81.0%) was not significantly different from control groups 3 (83.8%) and 4 (88.9%), while the number of group 2 oocytes with normal structures (43.5%) was significantly lower than groups 1 (P = 0.0004), 3 (P = 0.0002), and 4 (P = 0.025). These results suggest that cryopreservation of the prophase I human oocyte does not significantly increase abnormalities in the resulting meiotic spindle.

Objective: To examine the effect of high doses of gonadotropins on IVF outcome in normal (intermediate) responders., Design: Retrospective analysis of patients undergoing IVF therapy from 1990 to 1994 at our institution., Setting: Academic tertiary center., Patients: A homogeneous group of women that consisted of intermediate responders examined in their initial attempt and who received differing amounts of gonadotropins were examined., Interventions: All patients were stimulated using a combination of a GnRH-agonist and FSH and hMG and were allocated into two groups, based on the amount of gonadotropin administered initially (four or six ampules)., Main Outcome Measures: Implantation and pregnancy (clinical and ongoing) rates were compared., Results: There were no significant differences between patients receiving high doses versus those patients receiving lower doses of gonadotropins with regard to implantation and pregnancy rates., Conclusions: We conclude that high doses of gonadotropins have no detrimental effect on IVF outcome in normal (intermediate) responders.

Objective: To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation., Design: Randomized, prospective, double-blinded, placebo-controlled trial., Setting: One university-based tertiary infertility center and two private infertility centers., Patients: All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study., Interventions: Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound., Results: A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant., Conclusions: Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates.

Objective: To investigate the predictive value of sperm morphology assessed by strict criteria on IVF outcome., Design: Retrospective analysis of all IVF cycles (January 1987 to December 1992)., Main Outcome Measures: All patients were assigned to one of three groups based on sperm morphology: P-pattern (< 4% normal forms), G-pattern (4% to 14% normal forms), and N-pattern (> 14% normal forms). Morphology pattern was related to other semen characteristics and IVF outcome., Results: Despite corrective measures at oocyte insemination, the fertilization rate was significantly different among the three morphology groups, P < G < N. N-pattern sperm produced a mean fertilization rate over 85% regardless of low motility or concentration. In a cohort study, P-pattern cycles produced a lower implantation rate and lower ongoing pregnancy rate, independent of the lower fertilization rate., Conclusions: Strict morphology is an excellent biomarker of sperm fertilizing capacity, independent of motility and concentration. P-pattern sperm may denote a poorer prognosis for establishing a pregnancy, even after a satisfactory fertilization rate is achieved.

Objective: To examine the results of 7 years of thawed ET during natural or controlled cycles using exogenous steroids., Design: Retrospective evaluation to compare implantation and pregnancy rates with two protocols for transfer of cryopreserved-thawed pre-embryos., Setting: Tertiary care academic center., Patients: From January 1987 to December 1993, 521 patients who were < 40 years of age underwent 628 thawed embryo transfers., Main Outcome Measure: Pregnancy and implantation rates per thawed embryo transfer cycle., Results: A total 1,987 pre-embryos survived the thawing process and were used in 628 thaw-transfer cycles. Transfer was performed in a natural cycle 2 days after the LH peak or on day 17 of a programmed cycle using a GnRH-agonist and hormone replacement therapy protocol; 182 pregnancies were established (182/628; 29%). Similar pregnancy rates were seen in the natural cycle (112/398; 28%) and the programmed cycle (70/230; 30%). The implantation rates were similar in the two methods of transfer cycles (11.9% versus 10.3%, natural versus programmed cycle). There were no significant differences in clinical or ongoing pregnancy rates in a natural or programmed cycle, correcting for the number of cryopreserved-thawed pre-embryos transferred. Patient's age at the time of freezing and the number of cryopreserved-thawed pre-embryos transferred are more important determinants of pregnancy than the type of cycle in which transfer occurs., Conclusion: Transferring cryopreserved-thawed pre-embryos in a natural or programmed cycle yields similar pregnancy results.

In a retrospective study, we compared 118 patients with hydrosalpinx and 157 patients with bilateral salpingectomy entering an established in vitro fertilisation programme between 1988 and 1992. Patients with unilateral or bilateral hydrosalpinx had a lower clinical pregnancy rate, a higher miscarriage rate, and a lower ongoing pregnancy rate than patients with absent Fallopian tubes.

Objective: To determine the potential for in vitro maturation, fertilization, and cleavage after cryopreservation of immature, prophase I human oocytes., Design: Immature oocytes obtained in excess of the number required by the patient were randomized and cryopreserved at the prophase I stage or cultured as control. After thawing and maturation in vitro, test and control oocytes were inseminated with husband's sperm and evaluated for fertilization and cleavage in vitro., Setting: In vitro fertilization program., Patients: Consenting patients undergoing controlled ovarian hyperstimulation for the purposes of IVF., Main Outcome Measures: Rates of maturation to metaphase II, fertilization, and cleavage were compared between control and cryopreserved oocytes., Results: Upon thaw, 58.5% (72/123) of prophase I oocytes were viable. Control oocytes demonstrated a 74.8% (98/131) maturation rate to metaphase II, a 56.5% (52/92) fertilization rate, and an 11.5% (6/52) blastocyst rate. Cryopreserved oocytes showed a 83.3% (60/72) rate of maturation, a 57.7% (30/52) fertilization rate, and a 3.3% (1/30) blastocyst rate. No significant differences were noted between any of these parameters., Conclusions: These results demonstrate that prophase I oocytes from stimulated IVF cycles are able to survive cryopreservation and resume meiosis to achieve full nuclear maturation post-thaw. In addition, cryopreserved oocytes retain the same capacity for fertilization and development as control oocytes.

A retrospective study of 150 cycles of in-vitro fertilization (IVF) was undertaken to determine the impact of elevated serum progesterone in the early follicular phase of IVF cycles utilizing gonadotrophin-releasing hormone agonist (GnRHa) initiated in the follicular phase. A total of 127 patients identified as being at risk for poor response to stimulation were treated with a flare-up protocol of GnRHa combined with high dose follicle stimulating hormone (FSH). Patients were excluded for severe male factor requiring micromanipulation. Patients were stimulated with GnRHa beginning on cycle day 2, and high dose FSH beginning on cycle day 3. Some 85% of the cycles exhibited a rise of serum progesterone to a peak concentration of > 1.0 ng/ml (range, 1.2-4.2 ng/ml) during cycle days 2-6. When compared to cycles with no demonstrable progesterone rise, cycles with a rise were associated with a significantly decreased ovarian response: more ampoules of gonadotrophin were required (mean 26.8 versus 22.6, P < 0.05), lower peak oestradiol concentration was reached (mean 774 pg/ml versus 1030; P < 0.05), and fewer mature oocytes were harvested (mean 4.6 versus 7.5; P < 0.01). Among the different pregnancy outcomes (clinical pregnancy, no pregnancy, ongoing pregnancy, and miscarriage), there were no significant differences detected in the early follicular progesterone concentrations as measured by peak progesterone, progesterone area under the curve (days 2-6), and day of peak progesterone. The follicular phase initiation of GnRHa can result in significant elevations of serum progesterone in the early follicular phase, which may impair follicular recruitment and overall ovarian response.

Objective: To examine the results of a 5-year trial using cryopreservation to limit multiple pregnancy and optimize overall pregnancy per cycle., Design: Retrospective clinical evaluation of pregnancy rates (PRs) per cycle after freezing pronuclear stage human oocytes., Setting: Tertiary care academic center., Patients: Six hundred seventeen patients treated in 776 IVF-ET cycles from January 1987 to December 1991 (less oocyte donation cycles)., Main Outcome Measure: Pregnancy rate per cycle after transfer of pre-embryos developed from thawed pronuclear stage oocytes., Results: Three thousand seven hundred thirty-one oocytes were frozen. Of these, 2,039 were thawed. One thousand three hundred seventy-seven survived thawing (68%), and 1,370 were transferred after passing through syngamy to at least the first cleavage (68%). Of patients with thawing, 359 of 401 (90%) (449 of 505 cycles [89%]) received intrauterine transfer. One hundred thirty-three separate clinical pregnancies were established from 128 different cycles (128/449; 29%); 5 cycles had two thaws, each of which resulted in pregnancy. This PR is less than the overall fresh PR observed in patients who had excess pronucleate oocytes frozen (279/776; 36%) but is remarkably similar when adjusted for the number of pre-embryos transferred per cycle. The age of the patient at the time of cryopreservation and the number of quality of pre-embryos ultimately available for transfer were important factors in the establishment of pregnancy. The mode of ovarian stimulation and duration of cryostorage did not prove meaningful., Conclusions: Cryopreserved pronucleate oocytes that survive freezing, thawing, and progress through syngamy demonstrate a similar potential for implantation and pregnancy when compared with fresh conceptuses, the cumulative effect of which is an enhanced total PR per cycle.