Abstracts

Abstracts of Time to Conceive research

Biomarkers of ovarian reserve as predictors of fertility.

Anne Steiner, MD, MPH

As the ovary ages, the granulosa cell products antimullerian hormone (AMH) and inhibin, decline leading to a rise in early follicular phase follicle stimulating hormone (FSH) and subsequent shortening of the follicular phase and menstrual cycle length. These biomarkers of ovarian aging-chronologic age, menstrual cycle length, serum or urinary early follicular FSH, and AMH- have been proposed as potential measures of female fertility. Chronologic age has been the most commonly used biomarker to predict fertility following assisted reproductive technology (ART) and natural fertility. Menstrual cycle length also appears to be associated with fecundability in assisted and unassisted attempts to conceive. However, the value of menstrual cycle length as a predictor is limited by the low prevalence of short menstrual cycles, oral contraceptive use, and menstrual cycle irregularity. While FSH has been shown to be a predictor of assisted fertility, it appears to have low sensitivity for non-pregnancy and has unproven value as a predictor of unassisted fertility. AMH appears to have the most promise. Serum levels of AMH have been shown to be directly associated with the probability of conceiving following ART and naturally; however, there are no studies to date that examine AMH test characteristics, e.g. sensitivity, specificity, in the prediction of natural fertility and infertility. CONCLUSION: While historical and laboratory biomarkers of ovarian aging are associated with assisted and unassisted fertility, their value as predictors are unproven. These biomarkers require further study as “fertility tests” in the general population.

Abstract details

Date: March 2013

Journal: Journal of Assisted Reproductive Genetics

Article: Ovarian Reserve: Regulation and Implications for Women's Health. Proceedings of the 2012 NICHD-ASRM Conference
Volume: 30
Issue: 3
Pages: 285 - 292 

Impact of vaginal lubricants on fecundability.

Anne Steiner, MD, MPH, D. Leann Long, MS, Catherine Tanner, MD, Amy Herring, ScD

Over-the-counter vaginal lubricants have been shown to negatively affect in vitro sperm motility. To determine the impact of vaginal lubricant use during procreative intercourse on natural fertility, we conducted a prospective, time-to-pregnancy cohort study of 296 women, 30-44 years old, with no history of infertility, who had been trying to conceive for less than 3 months. Women completed a baseline questionnaire on vaginal lubricant use. They subsequently kept a daily diary for 3 months to record menstrual bleeding, intercourse, and vaginal lubricant use and conducted standardized pregnancy testing. Diary data were used to determine the fertile window and delineate lubricant use during the fertile window. A proportional hazards model was created to calculate fecundability ratios (FR) with any lubricant use in the fertile window considered as the timevarying exposure. Overall, 75 (25%) women stated in their baseline questionnaire that they use vaginal lubricants while attempting to conceive. Based on their prospective daily diary data, 57% of women never used a lubricant, 29% occasionally used a lubricant, and 14% used a lubricant frequently. Women, who used lubricants during the fertile window had similar fecundability to those women who did not use lubricants in unadjusted analyses (FR 1.37, 95% Confidence Interval (CI): 0.80, 2.36) and after adjusting for age, partner race, and intercourse frequency in the fertile window (FR 1.05, 95% CI: 0.59, 1.85). Lubricants are commonly used by couples during procreative intercourse. Lubricant use during procreative intercourse does not appear to reduce the probability of conceiving.

Abstract details

Date: June 2012

Presented at the Annual Meeting of the Society for Epidemiologic Research in Minneapolis, Minnesota, June 27-30, 2012.

Journal: American Journal of Epidemiology
Volume: 175
Issue: 11 (Supplement)
Pages: S88

Periconceptional changes in thyroid function.

Ursula Balthazar, MD, Anne Steiner, MD, MPH

BACKGROUND: Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.

METHODS: Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.

RESULTS: Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.

CONCLUSIONS: TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.

Abstract details

Date: March 2011

Presented at the Annual Meeting of the Society for Gynecologic Investigation in Miami, March 2011. Abstract selected for the President's Presenter Award.

Journal: Reproductive Sciences
Volume: 18
Issue: 3 (Supplement)
Pages: 270A

 

Urinary markers of ovarian aging and predicting natural fertility.

Anne Steiner, MD, MPH, Amy Herring, ScD, Juliana Meadows, PhD, Steven Hoberman, MS, Donna Baird, PhD, MPH 

OBJECTIVE: To generate estimates of the association between fecundability (probability of conceiving in a menstrual cycle) and urinary markers of ovarian aging, which are used in commercial fertility tests.

DESIGN: Prospective time-to-pregnancy study.

MATERIALS AND METHODS: Women, 30-44 years old, with no history of infertility, who had been trying to conceive for less than 3 months, provided early follicular phase serum and urine (N=99). They were followed until pregnancy or 6 months. While trying to conceive, women conducted standardized pregnancy testing and kept a diary to record bleeding and intercourse. Urine was analyzed for follicle stimulating hormone (FSH) and estrone 3-glucuronide (E1G); levels were creatinine-corrected. Cox models were used to calculate fecundability ratios. To adjust for patterns of intercourse, diary data were used to calculate day-specific probabilities of conception.

RESULTS: Serum and urinary FSH were highly correlated (r=0.85, p<0.01) as were serum estradiol and urinary E1G (r=0.78, p<0.01). Urinary FSH and E1G were not strongly associated with fecundability. 

Abstract details

Date: October 2010

Presented at the Annual Meeting of the American Society for Reproductive Medicine in Denver, October 2010.

Journal: Fertility and Sterility
Volume: 94
Issue:
4 (Supplement 1)
Pages:
S45

 

Impact of vaginal lubricants on fecundability.

Catherine Tanner, MD, Anne Steiner, MD, MPH

OBJECTIVE: Vaginal lubricants appear to negatively impact sperm motility in vitro; however, it is unknown if this translates into lower fertility in women using lubricants while trying to conceive. The aim of this study was to determine if vaginal lubricant use results in lower fecundability (probability of pregnancy in a given menstrual cycle).

DESIGN: Prospective time-to-pregnancy cohort study

MATERIALS AND METHODS: Women aged 30 to 45, with no known history of infertility, who identified themselves as trying to conceive for 3 months or less were eligible. Participants completed a baseline questionnaire, including demographic information, medical and behavior history, and lubricant use (type and frequency). Women were followed without intervention until a positive pregnancy test or until censoring at 6 months of trying to conceive. Data were analyzed using cox proportional hazard modeling to determine fecundability and to calculate fecundability ratios.

RESULTS: 125 participants with a total of 423 cycles were analyzed. 25.6% of women reported using lubricants while trying to conceive. Of these, 50% used KY brand lubricant, 21.8% used Astroglide brand lubricant, 12.5% used Pre-Seed, 6% used Silk and 12.5% used other brands of lubricant. Lubricant user fecundability was 17.5% while non-lubricant user fecundability was 15.6%. Median time to pregnancy was 3.3 cycles in lubricant users and 4.2 cycles in non-lubricant users. Unadjusted analyses revealed that lubricant users were 1.15 times (95%CI 0.68-1.95) as likely as non-lubricant users to conceive in each menstrual cycle at risk. Adjusting for age, race, partner body mass index, cycle length, previous parity and frequency of intercourse did not significantly alter the fecundability ratio.

CONCLUSIONS: Approximately 25% of women aged 30-45 use vaginal lubrication while trying to conceive. Lubricant use does not appear to significantly impact natural fecundability for these women.

Abstract details

Date: October 2009

Presented at the Annual Meeting of the American Society for Reproductive Medicine in Atlanta, October 2009.

Journal: Fertility and Sterility
Volume: 92
Issue:
Supplement 3
Page:
S42 

 

Refining estimates of natural fecundability in older, reproductive age women.

Catherine Tanner, MD, Anne Steiner, MD, MPH

OBJECTIVE: Natural fecundability (probability of conception per cycle) is most accurately determined through prospective, time-to-pregnancy studies. Previous studies have examined fecundability in women aged 35-40 as a group. We hypothesized that significant heterogeneity would exist within this group. The objective of this study was to refine fecundability estimates for older, reproductive age women.

DESIGN: Prospective time-to-pregnancy cohort study of women aged 30-45

MATERIALS AND METHODS: Women with no known history of infertility, who identified themselves as trying to conceive for 3 months or less completed a questionnaire at first menses following enrollment (N=131).

Women who conceived prior to the study visit completed a similar questionnaire upon notification of pregnancy (N=21).Women were followed without intervention until a positive pregnancy test or until censoring at 6 months of trying to conceive. Data were analyzed using cox proportional hazard models.

RESULTS: At time of abstract submission, 152 participants with a total of 548 cycles were analyzed. A statistically significant decrease in fertility was not observed until 38 years of age. After adjusting for confounders, 38-39 year olds were 25% (95% CI, 0.07-0.93) as likely as 30-31 year olds to conceive in each menstrual cycle at risk.

Abstract details

Date: October 2009

Presented at the Annual Meeting of the American Society for Reproductive Medicine in Atlanta, October 2009.

Journal: Fertility and Sterility
Volume: 92
Issue: 
Supplement 3
Pages: S17