Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study?
Summary Answer
There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise.
What Is Known Already
Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist.
Study Design, Size, Duration
This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed.
Participants/Materials, Setting, Methods
The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model.
MAIN RESULTS AND THE ROLE OF CHANCE: Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and > 50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%).
Limitations, Reasons for Caution
While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N = 107) or low 25(OH)D (N = 56) was small.
Wider Implications of the Findings
Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml).
STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests.
vitamin D fecundability, 25-hydroxyvitamin D conception, preconception vitamin D, vitamin D deficiency fertility, vitamin D supplementation pregnancy, serum vitamin D reproduction, vitamin D insufficiency, EAGeR trial vitamin D, vitamin D ovulation, preconception micronutrients
PMID 31665286 31665286 DOI 10.1093/humrep/dez170 10.1093/humrep/dez170
Cite this article
Jukic, A. M. Z., Baird, D. D., Weinberg, C. R., Wilcox, A. J., McConnaughey, D. R., & Steiner, A. Z. (2019). Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability. Human reproduction (Oxford, England), 34(11), 2163-2172. https://doi.org/10.1093/humrep/dez170
Jukic, A. M. Z., et al. "Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability." Human reproduction (Oxford, England), vol. 34, no. 11, 2019, pp. 2163-2172.
Keywords
Adult, Female, Fertility, Fertilization, Humans, Ovulation, Preconception Care, Pregnancy, Pregnancy Tests, Prospective Studies, Time-to-Pregnancy, Vitamin D/analogs & Derivatives/blood, Vitamin D, 25-hydroxyvitamin D, Conception, Fertility, Pregnant, Time to Pregnancy, Vitamin D
Are maternal preconception lipid levels associated with fecundability?Summary answerFecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels. Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity.Study design, size, durationA secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial. Participants/materials, setting, methodsA total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C Main results and the role of chanceThere were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (For: 0.76, 95% CI: 0.59, 0.97) and 29% (For: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol Limitations, reasons for cautionAlthough the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability. s of the findingsOur results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability.Study funding and competing interest(s)This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist.Trial registration number#NCT00467363.
To evaluate the clinical relevance of serum progesterone levels on the day of frozen embryo transfer (FET) and the dose of vaginal progesterone gel (Crinone) used for early luteal phase support (LPS) in artificial-cycle frozen embryo transfer (AC-FET). This single-center retrospective study analyzed 342 AC-FET cycles in patients aged 18-45 at Changhua Christian Hospital, Taiwan (April 2018-December 2022). Women aged 18-45 years undergoing AC-FET were included; cycles with >3 prior failed FETs, major comorbidities, donor oocytes, or missing outcome data were excluded. Pregnancy outcomes were assessed per cycle. Crinone (90 mg or 180 mg daily) was administered for 5 days after endometrial thickness ≥7 mm and progesterone <1.5 ng/mL. Serum progesterone was measured on the day of FET. Clinical pregnancy rates based on gestational sac (CPR-S), fetal heartbeat (CPR-H), and live birth rate (LBR) were evaluated. Receiver operating characteristic (ROC) evaluated the predictive value of serum progesterone levels. Associations between study variables and pregnancy outcomes were assessed using univariate and multivariable logistic regression. Comparisons of pregnancy outcomes between the high- and low-dose Crinone groups were further conducted using inverse probability of treatment weighting (IPTW) to adjust for baseline differences between dosage groups. Serum progesterone levels demonstrated poor predictive performance for CPR-S, CPR-H, and LBR (AUC 0.541-0.559) and were not independently associated with pregnancy outcomes in multivariable analyses. After adjustment using inverse probability of treatment weighting, a higher Crinone dose (180 mg vs. 90 mg) was significantly associated with higher CPR-S (OR, 1.87; 95% CI, 1.11-3.17; p = 0.020), CPR-H (OR, 2.11; 95% CI, 1.24-3.59; p = 0.006), and LBR (OR, 2.10; 95% CI, 1.31-3.38; p = 0.002). Serum progesterone levels measured on the day of FET did not predict pregnancy outcomes in AC-FET cycles using vaginal progesterone gel. A higher Crinone dose was associated with higher early clinical pregnancy rates compared with a lower dose.
Is there a difference in live birth rates at 24 months between infertile women with polycystic ovary syndrome (PCOS) who have normal versus abnormal glucose metabolism? Abnormal glucose metabolism did not significantly reduce live birth rates but was associated with increased obstetric complications. Women with PCOS are often at increased risk of glucose metabolism disorders. However, evidence about the impact of these disorders on pregnancy outcomes remains limited, particularly in Asian populations. This prospective cohort study was conducted at a reproductive care centre in Vietnam from June 2020 to August 2024. A total of 1208 women were enrolled. PARTICIPANTS/MATERIALS Eligible participants were infertile women aged 18-40 years diagnosed with PCOS (Rotterdam criteria). Comprehensive assessments included medical history, anthropometric measurements, endocrine evaluations, fasting plasma glucose (FPG), glycosylated haemoglobin (HbAlc), and oral glucose tolerance tests (OGTT). Participants were categorized into normal or abnormal glucose metabolism groups and monitored for live birth outcomes at 24 months from the first visit. MAIN Live birth rates at 24 months were comparable between women with normal versus abnormal glucose metabolism (52.7% vs 48.2%, P = 0.12). However, obstetric complications, including gestational diabetes mellitus (15.2% vs 28.0%, P < 0.001) and hypertensive disorders of pregnancy (2.3% vs 9.0%, P < 0.001), were more common in the group with abnormal glucose metabolism. In women who conceived naturally, greater waist circumference and higher Homeostatic Model Assessment of Insulin Resistance index were significantly associated with lower odds of live birth, whereas the presence of hyperandrogenism was associated with higher odds of live birth. No factors were significantly associated with live birth in the group that conceived via ovulation induction plus IUI. In the group that conceived through IVF or IVM, a higher BMI was significantly associated with a lower live birth rate. LIMITATIONS This single-centre study was conducted exclusively on infertile women from South-East Asia who had PCOS, potentially limiting generalizability to other populations. Additionally, metabolic assessments were only performed at baseline, preventing evaluation of longitudinal changes and their dynamic effects on reproductive outcomes. While no significant difference in live birth rates was observed between PCOS women with normal and abnormal glucose metabolism, the abnormal glucose metabolism group experienced higher rates of gestational complications. These findings underscore the importance of preconception metabolic screening and tailored fertility strategies that include targeted interventions to optimize reproductive and maternal outcomes in women with PCOS. This study was supported by My Duc Hospital. Lan N. Vuong reports funding from the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.108-2022.01); Speaker and conference fees; speaker and conference fees as well as a grant; speaker, conference, and scientific board fees outside the submitted work. All other authors declare no conflicts of interest. NCT04364087.
Serum progesterone (P) levels are critical for endometrial receptivity and implantation in frozen-thawed embryo transfer (FET) cycles. However, the prognostic role of P levels measured on the day of the β-human chorionic gonadotropin (β-hCG) pregnancy test has not been fully elucidated. This study aimed to evaluate the association between β-hCG day serum P levels and pregnancy outcomes in FET cycles. This retrospective cohort study included 621 FET cycles performed between January 2023 and December 2024, of which 79.5% were conducted using hormone replacement therapy (HRT) protocols and 20.5% using natural cycle (NC) protocols. Serum P levels were measured on the day of the β-hCG pregnancy test. Receiver operating characteristic (ROC) curve analysis was used to determine protocol-specific P thresholds for predicting ongoing pregnancy (OPR). Ongoing pregnancy was defined as a viable intrauterine pregnancy confirmed by ultrasound at or beyond 12 weeks of gestation. Multivariable logistic regression was applied to identify independent predictors of OPR. ROC analysis identified optimal P thresholds of 15.5 ng/mL in NC cycles (AUC 0.821) and 14.15 ng/mL in HRT cycles (AUC 0.595). Overall, 44% of patients had serum P levels below the protocol-specific threshold. OPR was significantly higher in patients with P levels above the threshold (NC: 63.0% vs. 12.8%; 48.1% vs. 31.9%; p < 0.001). Multivariable regression demonstrated that younger maternal age and higher β-hCG day P levels independently predicted OPR. In HRT cycles, blastocyst-stage transfer was also significantly associated with improved outcomes (OR = 0.27, 95% CI 0.13-0.59; p < 0.05). Serum P levels measured on the day of the β-hCG test are significantly associated with pregnancy outcomes in both HRT and NC FET cycles. Routine monitoring of late luteal P levels and individualized luteal phase support strategies may enhance clinical success rates.