Patricia M. McShane

Serum Prolactin and TSH in an In Vitro Fertilization Population: Is There a Link Between Fertilization and Thyroid Function?

AbstractPurpose: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. Methods: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. Results: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. Conclusion: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Effects of Lifetime Exercise on the Outcome of In Vitro Fertilization

OBJECTIVE: To estimate whether exercise before the first cycle of in vitro fertilization (IVF) affects cycle outcomes. METHODS: A total of 2,232 patients were prospectively enrolled before undergoing their first cycle of IVF for the treatment of infertility from 1994–2003 at three IVF clinics in the greater Boston area. The primary IVF outcomes of interest included successful live birth and four points of cycle failure: cycle cancellation, failed fertilization, implantation failure, and pregnancy loss. Unconditional logistic regression adjusting for observed confounders was used to quantify the relation between self-reported exercise and cycle outcome. RESULTS: In general, women who reported regular exercise were no more likely to have a live birth compared with those women who did not report exercise (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.7–1.0; P=.07). Women who reported exercising 4 hours or more per week for 1–9 years were 40% less likely to have a live birth (OR 0.6, CI 0.4–0.8) and were almost three times more likely to experience cycle cancellation (OR 2.8, CI 1.5–5.3) and twice as likely to have an implantation failure (OR 2.0, CI 1.4–3.1) or pregnancy loss (OR 2.0, CI 1.2–3.4) than women who did not report exercise. In general, women who participated in cardiovascular exercise had a 30% lower chance of successful live birth (OR 0.7, CI 0.6–0.9) than women who reported no exercise. CONCLUSION: Regular exercise before in vitro fertilization may negatively affect outcomes, especially in women who exercised 4 or more hours per week for 1–9 years and those who participated in cardiovascular exercise. LEVEL OF EVIDENCE: II-2

Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates

OBJECTIVE To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN Observational study. SETTING Three IVF clinics. PATIENT(S) One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S) In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S) Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S) At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S) Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.

Pregnancy outcomes following Tompkins metroplasty

Eighteen patients with poor reproductive histories and 2 patients with primary infertility underwent Tompkins metroplasty for a septate uterus. There were 19 pregnancies within 2 years of surgery, and 11 patients had at least 1 viable pregnancy, for an overall success rate of 55%. One of the infertile patients conceived and delivered. The average fecundability rate for the first 24 months was 0.078 (normal, 0.20). The cumulative pregnancy rate at 27 months was 94% by the life-table method. The group of patients (n = 14) with two or more losses and no other major risk factors for reproductive failure had higher fecundability and a better success rate (71%). The Tompkins metroplasty is a technically simple procedure with a success rate similar to that of the Jones procedure.

Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization

OBJECTIVE Polymorphic variants of the human progesterone receptor gene have been described, but their potential influence on in vitro fertilization outcome have not been studied. STUDY DESIGN DNA was available from 317 women (cases) who had >or=2 embryo transfers without a clinical pregnancy and from 288 women (control subjects) who became pregnant after 1 in vitro fertilization attempt. With protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism, amplification of polymorphism fragments, digestion with restriction enzymes, and gel visualization were performed. RESULTS Allele frequencies for the 2 variants were 15.5% for H770H T and 4.1% for +331A in cases and 17.9% and 3.6% in control subjects, respectively. Both polymorphisms were rare among non-white subjects. Possession of a H770H T allele was associated with a decreased risk for implantation failure, which was nonsignificant overall but significant in women aged <35 years (adjusted relative risk, 0.52 [95% CI, 0.28, 0.97]). Possession of a +331A allele was associated with an increased risk of implantation failure, which was nonsignificant overall but significant in women who weighed <135 pounds (adjusted relative risk, 3.85 [95% CI, 1.20, 12.30]). The +331G/A polymorphism tended to increase the risk for implantation failure in women with an H770H C/C genotype, but not in women with a C/T or TT genotype (P=.09). Among white women who were H770H C/C, there was a significant trend (P=.03) in the proportion of +331G/A carriers as the number of implantation failures increased, from 8.6% of women with 0 failed attempts to 40% among women with >or=5 failed attempts. CONCLUSION Although human progesterone receptor polymorphisms do not clearly affect the risk for implantation failure in most women who undergo in vitro fertilization, the likelihood that a woman carries the +331G/A human progesterone receptor polymorphism increases with the number of failed attempts at implantation.

Successful pregnancies with the use of laminaria tents before embryo transfer for refractory cervical stenosis

OBJECTIVE To determine whether laminaria tents are a safe and effective method of cervical dilatation in patients with a history of cervical stenosis and difficult ET. DESIGN Case reports describing two patients. SETTING Tertiary care, assisted reproduction practice. PATIENT(S) Two patients with cervical stenosis and a history of multiple failed cycles of IVF. INTERVENTION(S) Laminaria tents were placed intracervically before ET. MAIN OUTCOME MEASURE(S) Presence of a gestational sac and fetal heartbeat on ultrasound. RESULT(S) Successful clinical pregnancies occurred in both patients after laminaria placement and ET. CONCLUSION(S) Laminaria tent cervical dilatation appears to be a safe and effective option to assist ET in patients with a history of cervical stenosis.

Recent trends in assisted reproductive techniques and associated outcomes.

Objective We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. Methods We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994–1998. Results Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994–1995 to 22.5% for IVF and 28.0% for GIFT in 1997–1998 (P ≤ .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. Conclusion There were significant improvements in the success rates for IVF and GIFT from 1994–1998 that correlated with changes in ovulation induction regimens.

Basal hormone levels in women who use acetaminophen for menstrual pain

OBJECTIVE To compare basal gonadotropin and estradiol levels between women using acetaminophen versus those using no or other types of analgesics. DESIGN Observational study. SETTING Three IVF clinics in greater Boston. PATIENT(S) Three hundred eighty-six women accepted for their first IVF treatment who completed questionnaires recording medical history, including analgesic use for menstrual pain, and who had blood drawn during the menstrual phase of a cycle before treatment. MAIN OUTCOME MEASURE(S) Basal FSH, LH, and estradiol. RESULT(S) Basal hormone levels, especially LH, were lower for women who regularly used acetaminophen compared with women who used no medication or other types of analgesics. Lower hormone levels in acetaminophen users were consistently observed when women were subdivided by age, body mass index, smoking history, and degree of menstrual pain-features that might have influenced analgesic use or hormone levels. CONCLUSION(S) This study provides preliminary evidence that acetaminophen may lower gonadotropin and estradiol levels and offers a biologic basis for the epidemiologic observation that acetaminophen use may reduce the risk of ovarian cancer.

The effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation in an in vitro fertilization program

The purpose of this study was to examine the effects of baseline ovarian cysts on the clinical response to controlled ovarian hyperstimulation (COH) in an in vitro fertilization (IVF) program. Patients were divided into two groups: group 1 (n = 21) had cysts with mean diameters between 10 and 45 mm on their baseline ultrasound before COH, and group 2 (n = 76) had no ovarian cysts on their baseline ultrasound. There was no statistically significant difference between the groups in maximum serum estradiol, the number of follicles greater than or equal to 10 mm on the day of human chorionic gonadotropin (hCG) injection, the number of follicles greater than or equal to 15 mm on the day of hCG injection, the number of oocytes retrieved, and the number of embryos transferred. There was no difference between the groups in the cycle cancellation rate, in the pregnancy rate per cycle, or in the pregnancy rate per embryo transfer. This study suggests that small baseline ovarian cysts do not negatively impact on ovulation induction parameters or pregnancy rates in an IVF program.

Premature luteinization and in vitro fertilization outcome in gonadotropin/gonadotropin-releasing hormone antagonist cycles in women with polycystic ovary syndrome

OBJECTIVE To determine the incidence of premature luteinization in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian hyperstimulation (COH) with exogenous gonadotropin/GnRH antagonist (GnRH-a); to compare clinical outcomes in patients with and without premature luteinization. DESIGN Retrospective case series. SETTING IVF clinic. PATIENT(S) Thirty-five treatment cycles in 30 patients with PCOS. INTERVENTION(S) Controlled ovarian hyperstimulation with gonadotropin/GnRH-a protocol. MAIN OUTCOME MEASURE(S) Premature luteinization defined as a P concentration of >/=1.3 ng/mL on the day of hCG administration; number of oocytes and two pronuclei (2PN) embryos; implantation and clinical pregnancy rates (PR). RESULT(S) The incidence of premature luteinization was 28%. Compared with those without premature luteinization, patients with premature luteinization had a higher number of oocytes retrieved (24.1 +/- 13.3 vs. 12.0 +/- 5.9) and greater number of mature oocytes (19.7 +/- 11.7 vs. 9.5 +/- 4.5), respectively. The number of good quality embryos and embryos transferred was not significantly different between groups. Although implantation rates (56% vs. 40%) and clinical PRs (36% vs. 30%) were higher in patients without premature luteinization, the differences were not statistically significant. CONCLUSION(S) The patients with PCOS with premature luteinization had a higher number of oocytes retrieved and mature oocytes, and similar clinical PRs as patients with PCOS without premature luteinization.