Do elevated TSH levels predict early pregnancy loss in ART patients?

INTRODUCTION: The upper limit of normal TSH has been revised from 5 mIU/L to 2.5 mIU/L. We sought to evaluate IVF patients and the association between abnormal TSH and early pregnancy loss. METHODS: A retrospective study of patients who had TSH levels measured within the 2 weeks prior to their fresh autologous IVF cycles (2002-2014). Cohorts were stratified by oocyte age (<35, [35-38), [38-41), [41-43) and ≥43 years), and TSH level [(0-0.5], (0.5-2.5], (2.5-5], and (5-23) mIU/L]. Patients were followed until pregnancy loss or delivery. Model was assessed by chi-square of ANOVA with significance at p < 0.05. RESULTS: TSH was abnormally elevated (>5 mIU/L), mildly elevated ((2.5-5] mIU/L) or suppressed (≤0.5 mIU/L) in 46, 317 and 65 of the 1201 total cycles, respectively. Treatment resulted in 630 pregnancies, 524 clinical pregnancies and 409 deliveries. Pregnancy loss rates were increased in patients ≥38 yo (p < 0.001) but not [35-38) yo (p = 0.40) compared with those <35 yo. Early pregnancy loss rate was not associated with TSH level (p > 0.30) compared with euthyroid patients after adjusting for oocyte age. CONCLUSION: Early pregnancy loss rate in IVF patients appears to have no relation to recent TSH levels.

Maximum basal FSH predicts reproductive outcome better than cycle-specific basal FSH levels: waiting for a "better" month conveys limited retrieval benefits.

BACKGROUND: Elevated follicle stimulating hormone (FSH) is associated with poor vaginal oocyte retrieval (VOR) outcomes and cycle cancellations but intercycle variability in basal FSH reportedly does not predict ovarian response. METHODS: We conducted a retrospective cohort study of basal FSH (n = 15573 cycles) in couples (n = 9132) who initiated IVF cycle(s) with basal estradiol (E2) <100 pg/mL between 2002 and 2014 to reevaluate this hypothesis. The most recent (current) FSH, maximum FSH (Max FSH) and prior cycle maximum basal FSH (PMax FSH) were computed for each cycle. Metaphase II (MII) oocyte counts were modeled by age, stimulation type, prior peak E2 level, prior MII count, Max FSH, PMax FSH and current FSH. Antral follicle counts, pregnancy, clinical pregnancy and live birth rates were modeled as secondary outcomes. RESULTS: Max FSH level distinguished completed cycles from cancelled cycles better than PMax FSH or current FSH (AUC of 0.72, 0.71 and 0.61, respectively, p < 0.001). Fewer MIIs were retrieved (5.7 ± 3.8) in cycles with Max FSH >13 mIU/mL (n = 1475) than those with ≤13 mIU/mL (n = 11978) (11.6 ± 7.1) (p < 0.001). Max FSH was a better predictor of MII count than PMax FSH or current FSH after controlling for age, stimulation type, prior peak E2 level and prior MII count. Additional MIIs were retrieved on average in cycles with PMax FSH >13 mIU/mL (n = 1930) whose current FSH was ≤13 mIU/ml rather than >13 mIU/ml (p < 0.01) after controlling for age, cycle number and stimulation type. However, no improvement in pregnancy or live birth rate was detected. CONCLUSIONS: Max FSH is the best FSH-based predictor of ovarian reserve. Retrieval benefits from waiting for a "better" month appear to exist but are limited.

Endometrial pattern, but not endometrial thickness, affects implantation rates in euploid embryo transfers.

OBJECTIVE: To evaluate the relationship of endometrial thickness (EnT) and endometrial pattern (EnP) to euploid embryo transfer (ET) outcomes. DESIGN: Retrospective cohort. SETTING: Private academic clinic. PATIENT(S): Patients (n = 277; age 36.1 ± 4.0 years) whose embryos (n = 476) underwent aneuploidy screening with fresh (n = 176) or frozen (n = 180) ET from July 2010 to March 2014. INTERVENTION(S): The EnT and EnP were measured on trigger day and at ET. Patients were stratified by age and cycle type (fresh or frozen). Cycle data were combined at trigger day, but separated at ET day. MAIN OUTCOME MEASURE(S): Outcome measures were implantation rate, pregnancy rate, and clinical pregnancy rate. Analysis was conducted using χ(2) analysis and Fisher's exact test. RESULT(S): A total of 234 gestational sacs, 251 pregnancies, and 202 clinical pregnancies resulted from 356 cycles. The EnT (9.6 ± 1.8 mm; range: 5-15 mm) at trigger day (n = 241 cycles), as a continuous or categorical variable (≤8 vs. >8 mm), was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate. The EnT at day of fresh ET (9.7 ± 2.2 mm; range: 4.4-17.9 mm) (n = 176 cycles) or frozen ET (9.1 ± 2.1 mm; range: 4.2-17.7 mm) (n = 180 cycles) was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate. Type 3 EnP at trigger day was associated with increased serum progesterone at trigger and a decreased implantation rate, compared with type 2 EnP. The EnP at fresh or frozen ET was not associated with implantation rate, pregnancy rate, or clinical pregnancy rate. CONCLUSION(S): Within the study population, EnT was not significantly associated with clinical outcomes of euploid ETs. A type 3 EnP at trigger day suggests a prematurely closed window of implantation.

Female cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes?

OBJECTIVE: To evaluate the association between female cystic fibrosis (CF) carrier status and in vitro fertilization (IVF) response and outcomes. The presence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in male carriers has been associated with infertility, yet possible adverse effects on the ovarian function and reproductive outcomes of female carriers have not been studied to date. DESIGN: Retrospective cohort study. SETTING: Private academic, clinical reproductive center. PATIENT(S): Females<40 years of age who were screened for CFTR mutations and received IVF treatment between July 2002 and March 2013. INTERVENTION(S): Patients initiated controlled ovarian hyperstimulation with frequent monitoring, vaginal oocyte retrieval, fertilization, embryo transfer, and a pregnancy test. Various measures of IVF stimulation response and cycle outcome were evaluated for both carriers and noncarriers. MAIN OUTCOME MEASURE(S): Analysis was performed by logistic regression and Poisson regression. RESULT(S): IVF cycles (n=199) from CFTR mutation carrier patients (n=112) were analyzed. No significant differences in outcome were noted when carriers of different mutation loci were compared in aggregate with the noncarrier group (n=6,420 cycles from 3,555 patients). Significant differences were noted for some metrics when the carriers were grouped by mutation loci. CONCLUSION(S): Overall, no significant differences in stimulation response and cycle outcome were noted between female CFTR mutation carriers and noncarriers. Further research is needed to investigate whether the differences noted between specific CFTR mutation loci are clinically relevant and whether CFTR mutations may impact reproductive outcomes outside the context of assisted reproductive technologies.