James A. Grifo

Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation.

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.

Delivery rate using cryopreserved oocytes is comparable to conventional in vitro fertilization using fresh oocytes: potential fertility preservation for female cancer patients

OBJECTIVE To explore the use of oocyte cryopreservation as a fertility-conserving option. Cancer treatments administered during the reproductive and adolescent years can result in sterility. Previous fertility preservation efforts focused on embryo rather than oocyte storage because the latter was deemed inefficient. Recently, several large reports of healthy births resulting from the transfer of embryos derived from frozen/thawed oocytes have been published. We sought to establish an oocyte cryopreservation program at our center. DESIGN Twenty-three oocyte cryopreservation cycles were performed. Collected oocytes were cryopreserved by either the slow or the vitrification method. Approximately 1-4 months later, a programmed cycle of thawing/warming, fertilization with intracytoplasmic sperm injection, and ET was performed; cycle and pregnancy outcomes were assessed. SETTING University-based fertility center. PATIENT(S) Twenty-two infertile women. INTERVENTION(S) Oocyte cryopreservation. MAIN OUTCOME MEASURE(S) Oocyte survival, embryo development, pregnancy outcomes. RESULT(S) Oocyte survival, 2-pronuclei fertilization, and blastocyst formation rates were 92%, 79%, and 43%, respectively. Fourteen women became pregnant; one miscarried; 10 have delivered 13 viable infants, and three pregnancies are ongoing for an ongoing/delivered pregnancy rate of 57%. This result was not statistically different from cycles performed consecutively in age-matched controls using fresh, nonfrozen autologous or donor oocytes during a similar time period. CONCLUSION(S) Oocyte cryopreservation appears to be a viable option for fertility preservation in some centers.

Factors useful in predicting the success of oocyte donation: a 3-year retrospective analysis

OBJECTIVE To establish prognostic relevance of parameters assessed in oocyte donation cycles. DESIGN Retrospective analysis. SETTING Large university-based donor oocyte program. PATIENT(S) All oocyte recipient cycles achieving embryo transfer from September 1995 to October 1998. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Pregnancy. RESULT(S) Recipient age and reproductive status, day 9 and 12 serum estradiol (E(2)) levels and a progesterone (P) level obtained 2 days after initiation of hormonal therapy did not correlate with pregnancy. Endometrial thickness, but not endometrial pattern, was useful in predicting pregnancy outcome. The clinical pregnancy and live-birth rate in cycles where the endometrial thickness was less than 8 mm was significantly lower when compared to cycles with an endometrial thickness > or =9 mm. Cycles where optimal quality embryos were transferred had the highest implantation (36%), clinical pregnancy (63%) and live birth (54%) rates and these rates were significantly higher than those of cycles where only poor quality embryos were available for transfer (10% implantation, 17% clinical pregnancy, and 8% live birth rates, respectively; P<.05). CONCLUSION(S) The most reliable predictive factors for pregnancy in oocyte donation cycles are the quality of the embryos transferred and the recipients mid-cycle endometrial thickness. Recipient monitoring should minimally include ultrasound assessment of endometrial thickness.

Women with cancer undergoing ART for fertility preservation : a cohort study of their response to exogenous gonadotropins

Cancer patients produce similar numbers of oocytes after ovarian hyperstimulation compared with age-matched infertile controls, suggesting that malignancy does not adversely affect ovarian response.

Fertility after hysteroscopic resection of submucous myomas

STUDY OBJECTIVE To analyze fertility outcomes after resection of submucous myomas by operative hysteroscopy in infertile women. DESIGN Retrospective analysis (Canadian Task Force classification II-2). SETTING Academic tertiary referral center. PATIENTS Forty-one women (age 28-42 yrs) old with primary and secondary infertility, and histologically proved submucous myomas. Intervention. Hysteroscopic myomectomy performed with a rigid resectoscope. MEASUREMENTS AND MAIN RESULTS Of the 41 patients, 25 (60.9%) became pregnant overall and 20 (48.7%) delivered at term. Seventeen patients delivered a single fetus. Five delivered twins, three at term and two at 33 and 35 weeks. One woman delivered triplets at 31 weeks. The total delivery rate was 56.0%. Two women miscarried, at 6 and 8 weeks. One patient developed postoperative Ashermans syndrome. CONCLUSION Our results indicate that hysteroscopic myomectomy improves fertility in previously infertile women. Resection is a viable alternative to abdominal myomectomy for submucous myomas. (J Am Assoc Gynecol Laparosc 6(2):155-158, 1999)

Surviving childhood and reproductive-age malignancy: effects on fertility and future parenthood

Annually, more than 50,000 cancer diagnoses are made in the USA in patients under the age of 35 years. Despite this staggering statistic, medical advancements have substantially improved survival rates. Thus, for both male and female patients with cancer, quality-of-life issues, such as fertility preservation and parenthood, have become an essential component of treatment. Unfortunately, many of the treatments to eradicate malignant processes can also compromise reproductive function. In these cases, fertility preservation should be discussed and initiated with early treatment planning, to allow the best chance for future parenthood, when appropriate. The effects of cancer and cancer treatments on fertility and future parenthood, including health risks for patients, their gametes, and offspring are discussed.

Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies

Preimplantation genetic diagnosis and screening improves the chances of achieving a viable pregnancy, not only free of undesired single-gene defects but also aneuploidy. In addition, improvements in vitrification provide an efficient means of preserving embryos (blastocysts). By combining trophectoderm biopsy with recent improvements in vitrification methods, only those embryos that have proved themselves viable and potentially more competent are tested. Using array comparative genomic hybridization (aCGH) to assess all 24 chromosomes, aneuploidy rates were compared between day-3 blastomere biopsy and day-5 trophectoderm biopsy. Of those 1603 embryos, 31% were euploid, 62% were aneuploid and 7% not analysable. A significantly larger proportion of embryos were euploid on day-5 biopsy (42%) compared with day-3 biopsy (24%, P<0.0001). The number of euploid embryos per patient was not significantly different. Combining extended culture, trophectoderm biopsy and aneuploidy assessment by aCGH and subsequent vitrification can provide a more efficient means of achieving euploid pregnancies in IVF.

Simultaneous assessment of sperm chromatin condensation and morphology before and after separation procedures: effect on the clinical outcome after in vitro fertilization

OBJECTIVE To look for correlations between acridine orange (AO) staining and semen parameters before and after sperm separation procedures and to assess whether the AO test predicts fertilization or pregnancy outcomes after standard IVF and intracytoplasmic sperm injection. DESIGN Prospective study that simultaneously assesses sperm morphology and nuclear protein maturity on a cell-by-cell basis before and after preparative procedures. SETTING University teaching hospital. PATIENT(S) Men (n = 140) undergoing diagnostic semen analysis. MAIN OUTCOME MEASURE(S) Acridine orange fluorescence of sperm nuclei, semen parameters, IVF outcome. RESULT(S) In unprocessed samples, 90% of sperm with normal heads displayed green fluorescence (mature nuclear protein); significantly lower percentages of green fluorescence were observed in sperm with abnormal heads. The percentage of mature normal sperm in the specimen correlated with motility. Sperm maturity after swim-up or Percoll gradient was significantly improved for sperm with normal or abnormal heads. The percentage of mature normal sperm correlated with motility after either Percoll or swim-up. Neither the percentages of mature nuclei nor mature normal nuclei correlated with fertilization or pregnancy outcome. CONCLUSION(S) Nuclear protein maturation correlates with sperm motility and morphology. Because morphologically normal and motile sperm are more mature, separation procedures should generate a population of sperm with the highest fertilization capacity. Acridine orange staining, however, did not predict fertilization efficiency or pregnancy outcome in IVF cycles.

What is a normal thyroid-stimulating hormone (TSH) level? Effects of stricter TSH thresholds on pregnancy outcomes after in vitro fertilization

Using a thyroid-stimulating hormone (TSH) cutoff of 2.5 mIU/L or 4.5 mIU/L, no differences in the rates of clinical pregnancy, delivery, or miscarriage were observed in this large, retrospective cohort study of first-cycle IVF patients from 2005 through 2008, after controlling for age. Although lowering the TSH threshold to 2.5 mIU/L would result in a nearly fivefold increase in the number of women being classified as hypothyroid, the lack of differences in maternal clinical outcomes must be considered in the current controversy regarding the relative merits of lowering the upper limit of normal of TSH.

Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing

OBJECTIVE To determine whether undetected aneuploidy contributes to pregnancy loss after transfer of euploid embryos that have undergone array comparative genomic hybridization (aCGH). DESIGN Case-control study. SETTING University-based fertility center. PATIENT(S) Cases included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in miscarriage. Controls included 38 patients who underwent frozen euploid ET as determined by aCGH, resulting in a live birth. INTERVENTION(S) Next-generation sequencing (NGS) protocols were internally validated. Saved amplified DNA samples from the blastocyst trophectoderm biopsies previously diagnosed as euploid by aCGH were reanalyzed using NGS. Cytogenetic reports of the products of conception for 20 of the pregnancies resulting in miscarriage were available for comparison. MAIN OUTCOME MEASURE(S) The incidence of aneuploidy and mosaicism using NGS within embryos resulting in miscarriage and live birth. RESULT(S) Of euploid embryos analyzed by aCGH resulting in miscarriage, 31.6% were mosaic and 5.2% were polyploid by NGS. The rate of chromosomal abnormalities was significantly higher in embryos resulting in miscarriage (36.8%) than in those resulting in live births (15.8%). The rate of mosaicism was twice as high among embryos resulting in miscarriage than those resulting in live birth, but this was not statistically significant. Next-generation sequencing detected more cases of mosaicism than cytogenetic analysis of products of conception. CONCLUSION(S) Undetected aneuploidy may increase the risk of first trimester pregnancy loss. Next-generation sequencing may detect mosaicism and triploidy more frequently than aCGH, which could help to identify embryos at high risk of miscarriage. Mosaic embryos, however, should not be discarded as some can result in live births.