Glenn L. Schattman

Cumulative birth rates with linked assisted reproductive technology cycles.

BACKGROUND Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. METHODS We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment. RESULTS The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used. CONCLUSIONS Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).

Preimplantation diagnosis for p53 tumour suppressor gene mutations.

Preimplantation genetic diagnosis (PGD) was introduced for high-risk couples to avoid establishing affected pregnancies potentially requiring termination following prenatal diagnosis. This opens the possibility for PGD for late onset disorders with genetic predisposition, including inherited cancer predisposition, because only embryos free from the predisposing gene may be transferred back to the patient, with no potential risk for pregnancy termination. PGD was performed for two couples, one with maternally and one with paternally derived p53 tumour-suppressor mutations, 902insC in exon 8 and G524A in exon 5, respectively. This involved a standard IVF protocol, allowing oocytes or embryos to be tested prior to their transfer back to uterus. Maternal mutation was tested by sequential PCR analysis of the first and second polar bodies, removed following maturation and fertilization of oocytes, while paternal mutation analysis required embryo biopsy at the cleavage stage. To avoid misdiagnosis due to allele drop out, multiplex nested PCR was applied, involving p53 mutation analysis simultaneously with the linked short tandem repeats in intron 1. Of 10 oocytes tested in two PGD cycles for 902insC mutation, four unaffected oocytes were pre-selected for transfer yielding no clinical pregnancy. Of 18 embryos analysed in two cycles for G524A mutation, seven mutation-free embryos were detected, two of which were transferred in each cycle, resulting in a singleton pregnancy and birth of a mutation-free child. This is the first PGD for inherited cancer predisposition determined by p53 tumour suppressor mutations, resulting in a clinical pregnancy and birth of a child free from inherited cancer predisposition.

The role of embryonic origin in preeclampsia: a comparison of autologous in vitro fertilization and ovum donor pregnancies.

OBJECTIVE: To compare the risk of gestational hypertension and preeclampsia in pregnancies conceived through standard in vitro fertilization (IVF) using autologous oocytes with pregnancies conceived using donated oocytes. METHODS: We conducted a retrospective, matched cohort study of women undergoing IVF using autologous compared with donor oocytes between 1998 and 2005. Women with live births resulting from oocyte donor pregnancies were matched for age and plurality (singleton or twin) with women undergoing autologous IVF. Primary outcomes were the incidence of preeclampsia or gestational hypertension (with and without proteinuria) in the third trimester. Data on preterm delivery, low birth weight, and embryo cryopreservation were also recorded. RESULTS: Outcome data were available for 158 pregnancies, including 77 ovum-donor recipient pregnancies and 81 pregnancies using autologous oocytes. There were no differences in age, parity, and gestational type between the two cohorts. The incidence of gestational hypertension and preeclampsia was significantly higher in ovum-donor recipients compared with women undergoing autologous IVF (24.7% compared with 7.4%, P<.01, and 16.9% compared with 4.9%, P=.02, respectively). Ovum-donor recipients were more likely than women undergoing autologous IVF to deliver prematurely (34% compared with 19%). This association remained after controlling for multiple gestation (odds ratio 2.6, 95% confidence interval 1.04–6.3). Sixteen pregnancies from cryopreserved embryos were more likely to have hypertensive disorders of pregnancy (odds ratio 5.0, 95% confidence interval 1.2–20.5). CONCLUSION: Pregnancies derived from donor oocytes and cryopreserved–thawed embryos may be at a higher risk for hypertensive disorders of pregnancy. These findings inform future research and help counsel women using assisted reproductive technology. LEVEL OF EVIDENCE: II

Plasma Homocysteine, Fasting Insulin, and Androgen Patterns among Women with Polycystic Ovaries and Infertility

Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic‐appearing ovaries in an infertility setting.

A decision analysis of treatments for obstructive azoospermia.

BACKGROUND Treatments for post-vasectomy obstructive azoospermia include vasectomy reversal, microsurgical epididymal sperm aspiration (MESA) or percutaneous testicular sperm extraction (TESE) with IVF/ICSI. We examined the cost-effectiveness of these treatments. METHODS A decision analytic model was created to simulate treatment. Outcome probabilities were derived from peer-reviewed literature and the Society for Assisted Reproductive Technologies database. Procedural costs were derived from a sampling of high-volume IVF centers and the Medicare Resource Based Relative Value Scale. Indirect costs of complications, lost productivity and multiple gestation pregnancies were considered. Sensitivity analyses were performed. RESULTS Vasectomy reversal was more cost-effective than either MESA or TESE under all probability conditions. In 1999, vasectomy reversal demonstrated superior cost-effectiveness to TESE and MESA (

A decision analysis of treatments for nonobstructive azoospermia associated with varicocele.

19,633 versus

CLINICAL PRACTICE. Cryopreservation of Oocytes.

45,637 and

Atypical activation and fertilization patterns in humans

48,055, respectively, equivalent to

The parental origin of the distal pronucleus in dispermic human zygotes.

25,321 versus

Follicular flushing and in vitro fertilization outcomes in the poorest responders: a randomized controlled trial

58,858 and