B.A. Malizia

Cumulative Live-Birth Rates after In Vitro Fertilization

BACKGROUND Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couples primary concern is the chance of a live birth over an entire treatment course. METHODS We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return. RESULTS Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves (< 35 vs. > or = 40 years) were significantly different from one another (P<0.001). CONCLUSIONS Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility.

The cumulative probability of liveborn multiples after in vitro fertilization: a cohort study of more than 10,000 women

OBJECTIVE To estimate the cumulative probability of liveborn multiples after IVF to improve patient counseling regarding this significant morbidity. DESIGN Retrospective cohort study. SETTING Large academic-affiliated infertility practice. PATIENT(S) A total of 10,169 women were followed from their first fresh, nondonor IVF cycle through up to six fresh and frozen IVF cycles from 2000-2010. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Delivery of a liveborn infant(s). RESULT(S) After three IVF cycles the cumulative live birth rate (CLBR) was 53.2%. The singleton, twin, and triplet CLBRs were 38.0%, 14.5%, and 0.7%. After six IVF cycles the CLBR was 73.8%, with 52.8%, 19.8%, 1.3% for singletons, twins, and triplets. Of the 5,433 live births, 71.4% were singletons, 27.1% were twins, and 1.5% were triplets. Women more than 39 years had the lowest incidence of liveborn multiples with CLBRs of 5.2% after three cycles and 9.5% after six cycles. The twin CLBR doubled from cycles 1 through 3 with the rate of increase slowing from cycles 3 through 6. Although very low in absolute terms, the triplet CLBR also doubled from cycles 1 through 3 and doubled again from cycles 3 through 6. Of the 1,970 pregnancies that began as multifetal on ultrasound, 77.4% resulted in liveborn multiples. CONCLUSION(S) Providers should be aware of the cumulative probability of liveborn multiples to effectively counsel patients on this important issue. With nearly three-quarters of all women having live birth after up to six IVF cycles, it is encouraging to report a low incidence of liveborn multiples.

The human ovarian follicular fluid level of interleukin-8 is associated with follicular size and patient age

OBJECTIVE To investigate the relationship between interleukin-8 (IL-8) in the human ovarian follicle and follicular size, patient age, and fertility factors in IVF cycles. DESIGN Prospective study. SETTING University hospital research laboratory and infertility clinic. PATIENT(S) Women undergoing IVF with oocyte retrieval. INTERVENTION(S) Follicular fluid (FF) aspiration, oocyte isolation, FF storage, and experimental studies. MAIN OUTCOME MEASURE(S) Quantization of IL-8 by ELISAs and protein microarray; high-performance liquid chromatography (HPLC) followed by ELISA and Western blotting to evaluate alpha(2)-macroglobulin (alpha(2)M) bound IL-8; association of IL -8 to follicular size, patient age, and IVF outcomes. RESULT(S) Samples of FF from 63 patients contained an average of 629.59 pg/mL of IL-8 with 50%-70% bound to alpha(2)M. Large follicles contained higher levels of IL-8 than small follicles (937.34 vs. 86.97 pg/mL). The IL-8 concentration in the large follicles of women of young age was higher than that of older reproductive age women (1,373.61 vs. 673.29 pg/mL). There were no statistically significant associations found between IL-8 concentration and other IVF cycle factors or pregnancy outcome. CONCLUSION(S) Our findings indicate that IL-8 is present in FF, both in its free and alpha(2)M-bound state, and its concentration is correlated with follicular size and patient age.

Predicting personalized multiple birth risks after in vitro fertilization-double embryo transfer.

OBJECTIVE To report and evaluate the performance and utility of an approach to predicting IVF-double embryo transfer (DET) multiple birth risks that is evidence-based, clinic-specific, and considers each patients clinical profile. DESIGN Retrospective prediction modeling. SETTING An outpatient university-affiliated IVF clinic. PATIENT(S) We used boosted tree methods to analyze 2,413 independent IVF-DET treatment cycles that resulted in live births. The IVF cycles were retrieved from a database that comprised more than 33,000 IVF cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The performance of this prediction model, MBP-BIVF, was validated by an independent data set, to evaluate predictive power, discrimination, dynamic range, and reclassification. RESULT(S) Multiple birth probabilities ranging from 11.8% to 54.8% were predicted by the model and were significantly different from control predictions in more than half of the patients. The prediction model showed an improvement of 146% in predictive power and 16.0% in discrimination over control. The population standard error was 1.8%. CONCLUSION(S) We showed that IVF patients have inherently different risks of multiple birth, even when DET is specified, and this risk can be predicted before ET. The use of clinic-specific prediction models provides an evidence-based and personalized method to counsel patients.

Gestational hypothyroidism: development of mild hypothyroidism in early pregnancy in previously euthyroid women

OBJECTIVE To determine the proportion of euthyroid women attending a fertility practice who develop hypothyroidism in very early pregnancy (gestational hypothyroidism [GHT]), and to examine the association of GHT with exogenous gonadotropin treatment. DESIGN Retrospective cohort study. SETTING A private reproductive medicine practice. PATIENT(S) All healthy women (N = 94) with infertility or recurrent pregnancy loss, TSH level <2.5 mIU/L, negative thyroid peroxidase antibodies at initial evaluation, and not taking thyroid medication, who conceived during an 18-month period. INTERVENTION(S) Usual fertility care; 30 women who had received exogenous gonadotropins. MAIN OUTCOME MEASURE(S) Serum TSH level at the time of pregnancy detection. RESULT(S) Gestational hypothyroidism (TSH ≥ 2.5 mIU/L) developed in 23 of 94 women (24%). The mean increase in serum TSH level from initial evaluation to early pregnancy was 0.45 ± 0.08 [SE] mIU/L. There was a trend toward the association of GHT with use of exogenous gonadotropins. Gestational hypothyroidism was positively associated with initial prepregnancy TSH level. CONCLUSION(S) Euthyroid women may develop mild hypothyroidism in early pregnancy, especially after exogenous gonadotropin treatment. Appropriate vigilance will allow for timely levothyroxine treatment.