B. Sandler

Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility.

Female fertility declines with advancing age. To establish whether this age-related reproductive failure results from diminished oocyte quality or uterine/endometrial inadequacy we investigated ovum donation in 35 infertile women, aged 40 years or older (mean 42.7 [SE 0.3]) who had failed at attempts at conception with their own (self) oocytes. Oocytes were donated by 29 young individuals (mean age 33.4 [0.7]) undergoing in-vitro fertilisation (IVF). 8 (5.3%) pregnancies were achieved in 150 cycles of ovulation induction with self-oocytes and 2 (3.3%) in 60 such cycles by in-vitro fertilisation (IVF), but none attained viability. By contrast in 50 cycles with donated oocytes 28 (56%) pregnancies and 15 (30%) deliveries were realised (p less than 0.005). The rate of implantation per embryo transferred was higher (14.7%) with donated oocytes than that with self-oocytes (3.3%) (p less than 0.01). To further elucidate the contribution of age to reproductive outcome, pregnancy results were compared between the young donors and older recipients. Both donors and recipients shared oocytes from the same induced cohort. Rates for clinical pregnancy and delivery did not differ between donors (33% and 23%) and recipients (40% and 30%). Our data suggest that the age-related decline in female fertility is attributable to oocyte quality and is correctable by ovum donation. The uterus can adequately sustain pregnancies even when reproductive potential is artificially prolonged into the late 40s.

An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation

OBJECTIVE To determine if an elevated FSH:LH ratio predicts response in infertile patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN Retrospective study. SETTING The Division of Reproductive Endocrinology at the Mount Sinai Medical Center, New York, New York. PARTICIPANTS Seventy-four patients undergoing IVF-ET using similar protocols for COH with day 3 FSH, LH, and E2 testing available for analysis. All patients were < 41 years of age and had day 3 serum FSH < 15 mIU/mL (conversion to SI unit, 1.00). MAIN OUTCOME MEASURES Follicle-stimulating hormone:LH ratio, day 8 serum E2, peak serum E2, cancellation rate, pregnancy rate, and number and size of follicles. RESULTS An FSH:LH ratio > or = 3.6 (group I) predicted a poor response to COH (sensitivity 85.7% and specificity 95%). There were no significant differences regarding day 3 serum FSH and ampules of gonadotropins used for COH. Group I (ratio > or = 3.6) patients responded to COH with lower day 8 E2 (97 +/- 18 versus 319 +/- 36 pg/mL; conversion factor to SI unit, 3.671), peak E2 (422 +/- 115 versus 2,368 +/- 183 pg/mL), and fewer follicles > 15 mm (1.3 +/- 0.5 versus 17.1 +/- 1.0). In group I the cycle cancellation rate (12/14) was significantly higher than the group II cycle cancellation rate (2/60) and pregnancy rate in group II (ratio < 3.6) was 25%. CONCLUSIONS The FSH:LH ratio may increase before a dramatic increase in serum FSH is observed and appears to be a useful marker of ovarian reserve.

Severe ovarian hyperstimulation despite prophylactic albumin at the time of oocyte retrieval for in vitro fertilization and embryo transfer.

OBJECTIVE To report two cases of severe ovarian hyperstimulation syndrome (OHSS) despite the administration of 50 g IV albumin at the time of oocyte retrieval. Two previous published series failed to observe OHSS in patients receiving prophylactic IV albumin. DESIGN Case reports of two women undergoing controlled ovarian hyperstimulation with E2 > 4,500 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration who developed OHSS despite prophylactic albumin administration. SETTING The division of reproductive endocrinology at the Mount Sinai Medical Center. INTERVENTIONS Fifty grams IV albumin (200 mL of a 25% albumin solution) were administered over 30 minutes at the time of oocyte retrieval. MAIN OUTCOME MEASURES Prevention of interstitial fluid accumulation such as ascites, pleural effusions, and generalized edema. The other goals of albumin administration included avoiding hemoconcentration, renal insufficiency, and thrombotic complications. RESULTS The patients developed sequelae of severe OHSS requiring hospitalization, despite administration of IV albumin. CONCLUSION Albumin is a promising agent in the prevention of OHSS. However, until the basic pathophysiology of this disorder can be elucidated, the mechanism of its action will remain elusive. Attempts to quantify and report clinical outcomes and the ultimate completion of a prospective randomized study will assist in the prevention and management of this enigmatic disorder.

Failed fertilization in vitro: second day micromanipulation of oocytes versus reinsemination

OBJECTIVE To compare routine reinsemination with 2nd day micromanipulation in patients with poor day 1 fertilization. DESIGN A retrospective review of patient records. SETTING The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS Patients undergoing IVF-ET who had poor fertilization (< 35%) with standard insemination and underwent second day reinsemination of oocytes (group I, n = 84) compared with patients who underwent 2nd day micromanipulation with subzonal insemination (group II, n = 12). MAIN OUTCOME MEASURES Fertilization rate, cleavage rate, number of embryo transfers, and pregnancy rate. RESULTS Fertilization rate and cleavage rate were significantly higher in group II patients. Pregnancies per transfer were similar between groups I (3/21, 14.3%) and II (0/9, 0%). Second day fertilization was possible in 9 of 12 group II patients, and fertilization rate was higher than day 1 in all nine, however, only 50% achieved cleavage, and none achieved pregnancy. CONCLUSIONS Although micromanipulating oocytes that fail to fertilize may identify occult male factor infertility, may help the clinician plan future cycles, and may result in fertilization and even transfer of embryos in some cycles, there were no pregnancies in our series, and, for now, the clinical efficacy of this procedure remains in question.

Parental karyotype may reveal the source of a pregnancy loss even in the presence of a reportedly euploid fetal karyotype

OBJECTIVE To present a case of a fetal loss in which a normal fetal karyotype was obtained by banding studies. Identification of an abnormal maternal karyotype prompted subsequent reanalysis using fluorescence in situ hybridization (FISH). DESIGN Case report. SETTING University-affiliated IVF center. PATIENT(S) A 32-year-old woman, G1 P0, underwent a fetal loss at 8 weeks, and a suction curettage was performed. The patient had a previous first-trimester loss. INTERVENTION(S) The fetal tissue was evaluated by banding studies and found to be normal. Parental karyotyping was performed, and the fetal tissue was reanalyzed by FISH. MAIN OUTCOME MEASURE(S) Analysis of fetal karyotype by targeted FISH. RESULT(S) Maternal karyotype demonstrated a translocation [46,XX, t(8;10)(q24.3:q25.2)]. The fetal tissue was reanalyzed by FISH, and a segment of chromosome 10 was found on chromosome 8. CONCLUSION(S) A normal fetal karyotype, as measured by banding, does not exclude a genetic etiology for pregnancy loss. In this case, maternal translocation prompted the genetics laboratory to search for a small segment of translocated extra chromosomal material. This demonstrated that despite the finding of a normal fetal karyotype, in some cases parental karyotyping may have value.

Ovarian hyperstimulation syndrome complicated by uterine prolapse

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