Obesity has become an epidemic in developed societies. Retrospective studies suggest that obesity is associated with miscarriage in assisted reproduction. The objective of this study was to evaluate whether obesity is associated with miscarriage in spontaneous conception. We conducted a systematic review of published studies with pooled analysis. A literature review was performed. Studies in which fertility drugs or in vitro fertilization were used were excluded, unless data could be extracted for spontaneous conception. Data were compared for obese (body mass index [BMI]: ≥28 or 30 kg/m (2)), overweight (BMI: 25 to 29 kg/m (2)), and normal-weight (BMI: <25 kg/m (2)) women, with pooled odds ratios (ORs). Recurrent miscarriage data were analyzed separately. Six studies met the criteria for a cohort of 28,538 women. Pooled analysis revealed a higher miscarriage rate of 13.6% in 3800 obese versus 10.7% in 17,146 normal-BMI women (OR: 1.31; 95% confidence interval [CI], 1.18 to 1.46). Although the cohort was small, there was a higher prevalence of recurrent early miscarriage in obese versus normal-BMI women (0.4% versus 0.1%; OR: 3.51; 95% CI, 1.03 to 12.01). In women with recurrent miscarriage, there was a higher miscarriage rate in the obese versus nonobese women (46% versus 43%; OR: 1.71; 95% CI, 1.05). Based on retrospective studies, we concluded that obesity is associated with a higher miscarriage rate in women who conceive spontaneously. Larger prospective studies are urgently needed to verify these preliminary results.

Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical comorbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring.

Inflammation is a biologic process that mediates tissue effects including vasodilation, hyperemia, edema, collagenolysis and cell proliferation through complex immunologic pathways. In regards to the ovary, inflammation has key physiologic roles in ovarian folliculogenesis and ovulation. On the other hand inflammatory processes are subject to underlying pathology and if pushed, proinflammatory conditions may have a negative impact on ovarian follicular dynamics. Obesity and polycystic ovary syndrome (PCOS) serve as examples of conditions associated with chronic endogenous production of low-grade pro-inflammatory cytokines. Both conditions negatively impact ovarian folliculogenesis and ovulation. The pages that follow summarize the role of inflammation in normal ovarian follicular dynamics and evidence for its role in mediating the negative effects of obesity and PCOS on ovarian follicular dynamics. The review concludes with a summary supporting a role for lifestyle factors that favorably impact inflammatory process involved in obesity and PCOS to improve ovarian function.

Purpose Implantation failure is a major limiting factor of successful in vitro fertilization (IVF). The objective of this study was to determine if endometrial mechanical stimulation (EMS) by endometrial biopsy in the luteal phase of the cycle prior to embryo transfer (ET) improves clinical outcomes in an unselected subfertile population. Methods Double-blind, randomized controlled trial of EMS versus sham biopsy and odds of clinical pregnancy after IVF and embryo transfer. Secondary outcomes included spontaneous miscarriage and live birth. Results One hundred women enrolled and were randomized from 2013 to 2017. Enrollment was terminated after futility analysis showed no difference in clinical pregnancy between EMS versus control, 47.2% vs 61.7% (OR 0.55, 95% CI 0.25-1.23, p = 0.15). There were no significant differences between women who underwent EMS and those who did not in terms of positive pregnancy test 54.7% vs 63.8% (OR 0.69, 95% CI 0.31-1.53, p = 0.36), miscarriage 7.5% vs 2.1% (OR 3.76 95% CI 0.41-34.85, p = 0.22), or live birth 43.4% vs 61.7% (OR 0.48 95% CI 0.21-1.06, p = 0.07). Conclusions EMS in the luteal phase of the cycle preceding embryo transfer does not improve clinical outcomes in an unselected subfertile population and may result in a lower live birth rate. We caution the routine use of EMS in an unselected population.

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This study is not a clinical trial.

Purpose The purpose of this study was to evaluate whether outcomes are different if controlled ovarian stimulation (COS) is started in the luteal phase rather than the follicular phase. Methods A systematic review and meta-analysis was performed. Sixteen studies were included in the qualitative analysis, and eight studies with a total of 338 women were included in the quantitative analysis. Results Cycles initiated in the luteal phase were slightly longer (WMD 1.1 days, 95 % CI 0.39-1.9) and utilized more total gonadotropins (WMD 817 IU, 95 % CI 489-1144). However, no differences were noted in peak estradiol levels (WMD −411 pg/ml, 95 % CI −906-84.7) or in the total number of oocytes retrieved (WMD 0.52 oocytes, 95 % CI −0.74-1.7). There were slightly more mature oocytes retrieved in the luteal phase (WMD 0.77 oocytes, 95 % CI 0.21-1.3), and fertilization rates were significantly higher (WMD 10 %, 95 % CI 0.03-0.18). While only three studies reported pregnancy outcomes, no difference was noted in the FET pregnancy rates after COS in the luteal versus follicular phase (RR 0.95, 95 % CI 0.56-1.7).A post hoc power analysis revealed that a sample of this size was sufficient to detect a clinically meaningful difference of 2 oocytes retrieved with 93 % power.Conclusion Although initiating COS in the luteal phase requires a longer stimulation and a higher dose of total gonadotropin, these differences are not clinically significant. Furthermore, COS initiated in the luteal phase does not compromise the quantity or quality of oocytes retrieved compared to outcomes of traditional stimulation in the follicular phase.

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