A. Reh

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.

Impact of developmental stage at cryopreservation and transfer on clinical outcome of frozen embryo cycles.

Although several early IVF successes were achieved after transferring fully formed blastocysts, the majority of embryos replaced worldwide over the past 30 years have been at the cleavage stage. The programme at this study centre has previously found that delaying an embryo transfer to day 5 can reduce the chance for a high-order multiple gestation without compromising the pregnancy rate because fewer embryos can be replaced. To evaluate the impact of transfer day and embryonic stage at cryopreservation on cycle outcome, 6069 fresh and 706 frozen transfers from 2000-2006 performed at this study centre were retrospectively analysed. Approximately half of the fresh transfers were performed on day 3, with a shift to day-5 transfer over the study period with no change in cryopreservation incidence. Implantation, clinical pregnancy and live birth rates were significantly higher following day-5 transfer. When frozen-thawed embryos (2-cell to day-6 blastocysts) were transferred, acceptable pregnancy and live birth rates were achieved at all stages but thawed embryos transferred as day-5 blastocysts generated consistently higher clinical pregnancy and live birth rates. Transfer of embryos frozen on day 6 had the highest miscarriage and lowest live birth rates. Barring government regulation, an IVF programmes day for cryopreservation generally depends on its management of and success with fresh embryo transfer.

Optimizing embryo selection with day 5 transfer

OBJECTIVE To compare rates of implantation, pregnancy, miscarriage, multiple gestation, and selective reduction between patients undergoing day 5 (d5) and day 3 (d3) ETs. DESIGN Retrospective cohort study. SETTING University-based IVF center. PATIENT(S) The first d5 ET cycle of patients 42 years of age from 2003 to 2006 was compared with a historical control of first cycle d3 ET patients 42 years of age from 1996 to 1999 who would have met current d5 ET criteria. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Rates of implantation, clinical pregnancy, miscarriage, live birth, high order multiple pregnancy (HOMP), and selective reduction. RESULT(S) D5 ET patients had higher implantation rates (39% vs. 30%), with no difference in the no-transfer rate. D5 ET patients had lower rates of HOMP (2.5% vs. 11%) and HOMP delivery (0.7% vs. 3.5%), multiple pregnancy (27% vs. 33%), multiple delivery (19% vs. 26%), and twin delivery (18% vs. 23%). There were fewer selective reductions of HOMP with d5 ET (1.7% vs. 3.8%). CONCLUSION(S) Extended culture improves embryo selection through increased implantation, facilitating fewer embryos per transfer, which lowers multiple gestation rates and the need for HOMP reduction.

Evaluating the necessity for universal screening of prospective oocyte donors using enhanced genetic and psychological testing

BACKGROUND To minimize the potential for harmful inheritable conditions, donors are rigorously screened according to standard guidelines, yet such guidelines may not be sufficient to exclude egg donors with certain known inheritable conditions. We compared universal screening of oocyte donors with Tay-Sachs, Fragile X, karyotype and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) versus standard American Society of Reproductive Medicine (ASRM) guidelines that do not include such testing. METHODS In this 12 year retrospective cohort study, results of enhanced universal screening of all anonymous oocyte donor candidates from 1997 to 2008 at a university hospital oocyte donation program were reviewed. Primary outcomes were the frequency of oocyte donor candidates excluded as a result of enhanced universal screening (Tay-Sachs, Fragile X, karyotypic analysis and MMPI-2) versus basic screening according to ASRM guidelines. RESULTS Of 1303 candidates who underwent on-site evaluation, 47% passed the screening process, 23% were lost to follow-up and 31% were excluded. Genetic and psychological factors accounted for the most common reasons for candidate exclusion. Enhanced genetic screening excluded an additional 25 candidates (19% of all genetic exclusions) and enhanced psychological screening excluded an additional 15 candidates (12% of all psychological exclusions). Altogether enhanced screening accounted for 40 candidates (10%) of the total pool of excluded candidates. CONCLUSIONS Although our study is limited by its retrospective nature and center-specific conclusions, we show that enhanced comprehensive screening can exclude a significant number of candidates from an oocyte donor program and should be encouraged to assure optimal short-term and long-term outcomes for pregnancies achieved through oocyte donation.

Are gonadotropin-releasing hormone agonists losing popularity? Current trends at a large fertility center

OBJECTIVE To explore the long- and short-term trends in LH-suppression protocol use and patient profile characteristics. DESIGN Descriptive study, retrospective cohort. SETTING Large, university-based IVF center. PATIENT(S) Four thousand five hundred one fresh IVF cycles categorized by use of GnRH antagonist, luteal GnRH agonist, and follicular microdose GnRH agonist. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Frequency of use of LH-suppression protocol, patient and cycle characteristics, and outcomes at 10-year (1996-2005), 5-year (2001-5), and 3-year intervals (2004-6). RESULT(S) In both the <40 and >or=40 age groups, GnRH antagonist use increased from 2001 to 2005, while luteal GnRH agonist and microdose use decreased. The most recent luteal agonist patients were better responders and had higher implantation, clinical pregnancy, and delivery rates. Antagonist patients in the <40 and >or=40 age groups had a better response in 2005 than in 2001 with higher clinical pregnancy rates. Microdose patients responded worse in 2005 than in 2001, although pregnancy rates did not change significantly. Such trends were echoed from 2004 to 2006. CONCLUSION(S) The target population for GnRH antagonist has broadened to include younger, normal responders in addition to the traditional poor responder. Luteal agonist and microdose protocols are chosen less frequently and remain targeted toward good and poor responders, respectively.