Frontiers in Reproductive Health, 6, 1508151, 2024
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Kahn, L. G., Loo, E., Mishra, G. D., & Stanford, J. B. (2024). Editorial: Opportunities and challenges of human preconception research. Frontiers in reproductive health, 6, 1508151. https://doi.org/10.3389/frph.2024.1508151
Kahn LG, Loo E, Mishra GD, Stanford JB. Editorial: Opportunities and challenges of human preconception research. Front Reprod Health. 2024;6:1508151. doi:10.3389/frph.2024.1508151
Kahn, L. G., et al. "Editorial: Opportunities and challenges of human preconception research." Frontiers in reproductive health, vol. 6, 2024, pp. 1508151.
Stanford JB et al., 2026·Frontiers in Reproductive Health
Background The total fertility rate (TFR) in most developed countries has been declining for decades. In the United States (U.S.), the total fertility rate has remained below replacement level since 2007. Subfertility affects at least 15% of women or couples over their reproductive lifespan and contributes to reduced TFR. Restorative reproductive medicine (RRM) is a medically based approach to subfertility care that can be delivered in primary care settings to increase live birth rates. Objective To estimate the theoretical impact of use of RRM among subfertile couples in the United States. Methods We conducted a simulation study. Model inputs included the number of women of reproductive age in the United States by 5-year age groups; current age-specific and total fertility rates; the proportion of women in each age group with subfertility; estimated spontaneous live birth rates among women with subfertility; and age-specific crude live birth rates with RRM treatment. We evaluated fifteen scenarios two different varying assumptions for spontaneous conception (25% vs. 50%), two levels of RRM utilization among subfertile women (20% vs. 50%), three different estimates of the number of subfertile women who would be potentially eligible for RRM treatment, and 4 different levels of effectiveness (live birth) from RRM treatment. Results The baseline TFR in the United States was 1.77 during 2015-2019, and 13.5% of women ages 20-44 were estimated to have subfertility. In a conservative scenario (50% spontaneous births; 20% RRM utilization; married women trying to conceive for at least 12 months, 20.7% RRM live births), the TFR increased to 1.79, representing a 1.0% relative increase (absolute +0.02). In an optimistic scenario (25% spontaneous births; 50% RRM utilization; all subfertile women), the TFR increased to 2.02, a 14.5% relative increase (absolute +0.26), approaching replacement-level fertility. Conclusion Simulation results suggest that expanding access to RRM within primary care settings could meaningfully increase the U.S. TFR, by reducing unresolved subfertility. Realizing this potential would require policy and health system changes to address workforce capacity, insurance coverage, and equitable access. These findings underscore the potential contribution of non-IVF fertility care pathways in addressing population-level fertility decline.
Barbato M et al., 2026·Frontiers in Reproductive Health
Couple infertility is a common clinical condition that is too often treated with assisted reproductive techniques (ARTs) without a proper evaluation of both male and female factors. To improve the likelihood of natural conception, fertility awareness methods (FAMs) are widely used. We performed a multicenter prospective study enrolling couples with primary idiopathic infertility who were seeking natural conception. Participants were followed for 12 months using FAMs, and their outcomes were compared with those of couples who only used ARTs. The aim of our study was to evaluate the pregnancy rate after 12 months among couples with idiopathic infertility using FAMs compared with those who immediately pursued ARTs. We evaluated 41 couples in the FAM group and 56 couples in the ART group. In the FAM group, we reported a pregnancy rate (PR) of 51.22%. Among women aged <34 years, we reported a PR of 90.9%, while it decreased to 36.7% among women aged 35-39 years. In the ART group, 10 couples achieved pregnancy (PR 17.8%). Within this group, we reported a PR of 30% among women aged <34 years and 17.4% among women aged 35-39 years. After 12 months of unprotected intercourse without spontaneous conception in women younger than 35 years or after 6 months in women aged 35-39 years, couples should undergo a complete multidisciplinary diagnostic evaluation involving both the male and female partners. If a diagnosis of idiopathic infertility is established at the end of this process, couples (especially younger ones) may be advised to wait an additional 12 months while using FAMs, as no advantage has been observed with direct access to ARTs. They could then be referred to ART if a spontaneous pregnancy is not achieved during this period.
Sánchez-Méndez JI et al., 2025·Front Reprod Health
Assisted reproductive technologies (ART) are widely used to address infertility; however, they are costly, associated with medical risks, and often yield suboptimal clinical outcomes. Natural Procreative Technology, also known as NaProTechnology (NPT), provides a systematic and integrative approach to infertility by thoroughly identifying and treating underlying medical conditions to restore the couple's natural fertility potential. Despite its promise, real-world data on NPT effectiveness remain limited. The objective of this study is to evaluate the take-home baby rate in a large population of infertile couples treated with NPT and to synthesize findings from previously published studies. A retrospective cohort study was conducted involving 1,310 infertile couples treated at a specialized fertility clinic in Spain over a 5-year period. Participants presented with primary or secondary infertility or recurrent pregnancy loss. Clinical data, diagnoses, and outcomes were analyzed, including surgical interventions and treatment duration. The mean age of women and men was 35.0 (SD 4.4) and 36.9 (SD 5.3) years, respectively. Primary infertility was the most common subtype (73.5%), the median infertility duration was 24 months, and prior ART attempts were recorded in 27.5% of couples. Mean number of diagnoses per couple was 2.5 (SD 1.3). The crude take-home baby rate was 35.3% (N = 463). Independent predictors of successful take-home baby included female age, recurrent pregnancy loss as the reason for consultation, duration of infertility, and the presence of endometriosis, hormonal dysfunction, male factor, and endometrial disorders as diagnoses. Considering a median duration of NPT of 10.9 months (range 8.1-17.0), the adjusted cumulative take-home baby rate was 62.1%. Rates varied significantly by female age, with higher success 83.7% at 18-30 years, 53.3% at 36-40 years, and 24.4% over 40 years. A sensitivity analysis was performed to assess the impact of dropout assumptions on cumulative pregnancy rates. Nearly one-third of patients underwent surgery, most commonly hysteroscopy and/or laparoscopy. In this cohort, NPT was associated with a notably high take-home baby rate in an infertile population with unfavorable prognostic factors, including advanced maternal age, prolonged duration of infertility, or previous failed attempts at conventional ART procedures.
Boyle P et al., 2024·Frontiers in Reproductive Health
Low serum estradiol in early pregnancy is associated with an elevated risk of miscarriage. We sought to determine whether efforts to restore low blood estradiol via estradiol or dehydroepiandrosterone (DHEA) supplementation would reduce the risk of miscarriage as part of a multifactorial symptom-based treatment protocol. This retrospective cohort study included women with low serum estradiol levels in early pregnancy, defined as ≤50% of reference levels by gestational age. Estradiol or DHEA were administered orally, and the primary outcome measure was serum estradiol level, in reference to gestational age. The secondary outcome measures included miscarriage, birth weight, and gestational age at birth. We found no significant effect of estradiol supplementation on serum estradiol levels referenced to gestational age, while DHEA supplementation strongly increased estradiol levels. For pregnancies with low estradiol, the miscarriage rate in the non-supplemented group was 45.5%, while miscarriage rate in the estradiol and DHEA supplemented groups were 21.2% (p = 0.067) and 17.5% (p = 0.038), respectively. Birth weight, size, gestational age, and preterm deliveries were not significantly different. No sexual abnormalities were reported in children (n = 29) of DHEA-supplemented patients after 5-7 years follow-up. In conclusion, DHEA supplementation restored serum estradiol levels, and when included in the treatment protocol, there was a statistically significant reduction in miscarriage.