Mark D. Hornstein

The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer

OBJECTIVE To select patients for day 3 vs. day 5 embryo transfer. DESIGN Retrospective analysis of assisted reproduction technology (ART) cycles comparing outcomes of day 3 and day 5 transfers. SETTING ART program of Brigham and Womens Hospital. PATIENT(S) Patients with day 3 or day 5 embryo transfers (n = 221 and 141, respectively). INTERVENTION(S) Cycles with eight or more zygotes were stratified by the number of eight-cell embryos available on day 3 (none, one or two, or three or more). MAIN OUTCOME MEASURE(S) Number of blastocysts, implantation rates, ongoing pregnancy rates, and number of fetal heart beats. RESULT(S) With no eight-cell embryos on day 3, 0% and 33% pregnancies resulted from day 5 vs. day 3 transfers. With one or two eight-cell embryos on day 3, ongoing and high order multiple rates were not different between day 3 and day 5 transfers. With three or more eight-cell embryos, day 5 transfer resulted in a decrease in multiple gestations but no difference in ongoing pregnancy rates compared with day 3 transfer. CONCLUSION(S) With no eight-cell embryos on day 3, a day 3 transfer is warranted. With one or two eight-cell embryos, any benefit of day 5 transfer appears to be equivocal. With three or more eight-cell embryos, day 5 transfer is recommended.

Effects of endometriomas on ooccyte quality, embryo quality, and pregnancy rates in in vitro fertilization cycles : A prospective, case-controlled study

Purpose:The effect of endometriomas on oocyte quality, embryo quality, and pregnancy rates in in vitro fertilization (IVF) cycles was evaluated.Methods:Forty-five women had “chocolate” cysts aspirated at the time of oocyte retrieval, and cyst fluid CA 125 levels were measured to ascertain presence of “true” endometriomas. Fifty-seven women without any complex cysts at the time of oocyte retrieval served as controls. IVF cycle outcome parameters were compared between the two groups.Results:Women with endometriomas experienced a significantly higher rate of early pregnancy loss compared to controls (47 vs 14%). There was also a trend toward fewer oocytes retrieved and fewer embryos reaching at least the four-cell stage 48 hr after retrieval in patients with true endometriomas vs controls.Conclusions:The presence of endometriomas at the time of oocyte retrieval is associated with increased rates of early pregnancy losses. The number of oocytes retrieved and the embryo quality may also be affected adversely in the presence of endometriomas.

Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up☆

OBJECTIVE To assess post‐treatment effects in endometriosis patients of a 12‐month course of GnRH agonist alone or with one of three “add‐back” regimens. METHODS This is a post‐treatment follow‐up analysis of a randomized, double‐masked, placebo‐controlled 52‐week trial. All patients had received monthly leuprolide acetate and were randomized to one of four groups: A—daily placebo; B—daily norethindrone acetate 5 mg; C—daily norethindrone acetate 5 mg and conjugated equine estrogens 0.625 mg; and D—daily norethindrone acetate 5 mg and conjugated equine estrogens 1.25 mg. Of 201 patients enrolled in the initial trial, 123 completed at least 280 days of therapy and entered the follow‐up period. Physical findings and symptoms were quantified, and lumbar spine bone mineral density was determined at intervals for up to 12 and 24 months post‐therapy. RESULTS Symptom and pelvic examination scores remained significantly below baseline for at least 8 months after completion of therapy for all four groups (P < .05). Findings were not affected by endometriosis scores noted on screening laparoscopy. Mean bone mineral density values remained at or above baseline in all add‐back groups. The significant mean loss in bone density in group A during therapy reversed slowly and had not returned to baseline at the final follow‐up visit (P < .001). CONCLUSION GnRH agonist and norethindrone acetate alone or combined with low‐dose conjugated equine estrogens administered to symptomatic endometriosis patients for 12 months provides extended pain relief and bone mineral density preservation after completion of therapy.

Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis

OBJECTIVE To evaluate whether the presence of antiphospholipid antibodies among women undergoing IVF affects the likelihood of IVF success. DESIGN A meta-analysis of seven eligible studies on antiphospholipid antibodies and IVF outcome. MAIN OUTCOME MEASURE(S) Odds ratios (ORs) and 95% confidence intervals (CIs) of an association between the presence of antiphospholipid antibodies and both clinical pregnancy and live birth from IVF. RESULT(S) There was no significant association between antiphospholipid abnormalities and either clinical pregnancy (OR 0.99; 95% CI 0.64-1.53) or live birth (OR 1.07; 95% CI 0.66-1.75) in IVF patients. CONCLUSION(S) The measurement of antiphospholipid antibodies is not warranted in patients undergoing IVF.

Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles

OBJECTIVE To determine if multinucleation in normally fertilized embryos is indicative of poor developmental or clinical pregnancy prognosis and to examine the ovulation induction characteristics associated with multinucleation. DESIGN Retrospective review. SETTING A tertiary care institution. PATIENT(S) Patients undergoing IVF-ET cycles (exclusive of other assisted reproductive technologies). MAIN OUTCOME MEASURE(S) Cycles in which embryos had at least 1 multinucleated blastomere were compared with cycles in which all blastomeres exhibited no nucleus or a single nucleus (control). RESULT(S) When >50% of transferred embryos contained multinucleated blastomeres there was a significant reduction in implantation (3.4% vs. 14.7%), clinical pregnancy (9.1% vs. 29.1%), and live birth rates (7.5% vs. 27.6%) when compared with transfers of control embryos. In conjunction with this finding, multinucleate cycles had higher E2 levels and more follicles on the day of hCG administration, a higher number of oocytes retrieved, a higher fertilization rate, and more embryos transferred per patient than did the cycles that produced control embryos. When multinucleated embryos were present, but not transferred, the developmental capacity of the sibling embryo was reduced. CONCLUSION(S) The evaluation of nuclear status using simple light microscopy is predictive of embryo developmental capacity and should be included in the embryo scoring system. The presence of multinucleated blastomeres in normally fertilized embryos is associated with a more effusive response to gonadotropin therapy and is indicative of a poor developmental outcome and lower clinical pregnancy rates.

Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain

OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and, furthermore, to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis. DESIGN Double-blind, prospective, multicenter, clinical trial. SETTING Fifteen reproductive endocrine clinics throughout the United States. PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis. INTERVENTIONS Patients were assigned randomly to 3 months nafarelin followed by 3 months of placebo (n = 91) or to 6 months nafarelin (n = 88) in a prospective, randomized, double-blind multicenter trial. Patients were followed for 12 months after cessation of therapy. MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings. RESULTS Pain scores dropped significantly by the end of treatment in both groups. Symptoms recurred in both groups, and pain scores gradually increased during the follow-up period but always remained below baseline in both groups. No significant difference in efficacy was noted between the groups. A total of 26% of patients in each group underwent retreatment for recurrent symptoms. CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis. One year follow-up demonstrated continued pain relief but with gradual return of symptoms.

Racial and ethnic disparities in assisted reproductive technology outcomes in the United States

OBJECTIVE To evaluate ethnic differences in assisted reproductive technology (ART) outcomes in the United States. DESIGN Historical cohort study. SETTING Clinic-based data. PATIENT(S) A total of 139,027 ART cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System online database for 2004-2006, limited to white, Asian, black, and Hispanic women. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Logistic regression was used to model the odds of pregnancy and live birth; among singletons and twins, the odds of preterm birth and fetal growth restriction. Results are presented as adjusted odds ratios, with white women as the reference group. RESULT(S) The odds of pregnancy were reduced for Asians (0.86), and the odds of live birth were reduced for all groups: Asian (0.90), black (0.62), and Hispanic (0.87) women. Among singletons, moderate and severe growth restriction were increased for all infants in all three minority groups (Asians [1.78, 2.05]; blacks [1.81, 2.17]; Hispanics [1.36, 1.64]), and preterm birth was increased among black (1.79) and Hispanic women (1.22). Among twins, the odds for moderate growth restriction were increased for infants of Asian (1.30) and black women (1.97), and severe growth restriction was increased among black women (3.21). The odds of preterm birth were increased for blacks (1.64) and decreased for Asians (0.70). CONCLUSION(S) There are significant disparities in ART outcomes according to ethnicity.

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.

Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program

This is a report of three cervical pregnancies, one of which was a heterotopic twin cervical pregnancy that occurred in combination with a single intrauterine pregnancy. Transvaginal ultrasound examination was sufficient to establish the diagnosis in two of three patients, and MRI scanning was conclusive in the third. Early diagnosis lead to intervention before 7 weeks gestation in all cases with no complications. The incidence of cervical pregnancy may be higher in IVF-ET than recognized previously.

Physical activity and semen quality among men attending an infertility clinic

OBJECTIVE To examine the association between regular physical activity and semen quality. DESIGN Prospective cohort study. SETTING Couples attending one of three IVF clinics in the greater Boston area during 1993-2003. At study entry, male participants completed a questionnaire about their general health, medical history, and physical activity. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using generalized estimating equations models, accounting for potential confounders and multiple samples per man. PATIENT(S) A total of 2,261 men contributing 4,565 fresh semen samples were enrolled before undergoing their first IVF cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Semen volume, sperm concentration, sperm motility, sperm morphology, and total motile sperm (TMS). RESULT(S) Overall, none of the semen parameters were materially associated with regular exercise. Compared with no regular exercise, bicycling ≥ 5 h/wk was associated with low sperm concentration (OR 1.92, 95% CI 1.03-3.56) and low TMS (OR 2.05, 95% CI 1.19-3.56). These associations did not vary appreciably by age, body mass index, or history of male factor infertility. CONCLUSION(S) Although the present study suggests no overall association between regular physical activity and semen quality, bicycling ≥ 5 h/wk was associated with lower sperm concentration and TMS.