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Background The use of progestin (P) during ovarian stimulation is effective in blocking the luteinizing hormone (LH) surge in women with normal ovarian reserve, however, its effects have not been determined in poor responders. This study aimed to explore the follicular dynamics in P-primed minimal stimulation in poor responders. Methods A total of 204 infertile women with diminished ovarian reserve were allocated into the medroxyprogesterone acetate (MPA) group or the natural-cycle control group in an alternating order. MPA (10 mg) was administered daily beginning from the early follicular phase and a low dose of hMG was added in the late follicular phase if the serum FSH level was lower than 8.0mIU/ml. When a dominant follicle reached maturity, triptorelin 100 μg and hCG 1000 IU were used for trigger, and oocytes were retrieved 34-36 h later.All viable embryos were cryopreserved for subsequent frozen embryo transfer. Natural cycle IVF was used as controls. Results Compared with the natural cycle group, the MPA group exhibited a larger pre-ovulatory follicle (18.7 ± 1.8 mm vs 17.2 ± 2.2 mm), a longer follicular phase (13.6 ± 3.6 days vs 12.3 ± 3.2 days), and higher peak oestradiol values (403.88 ± 167.16 vs 265.26 ± 122.16 pg/ml), while maintaining lower LH values ( P  < 0.05). The incidences of spontaneous LH surge and premature ovulation decreased significantly (1.0% vs 50%; 2% vs. 10.8%, respectively; P  < 0.05). A greater number of oocytes and viable embryos were harvested from the MPA group than from the natural cycle group ( P  < 0.05). Moreover,the clinical pregnancy rate was slightly higher in the MPA group than in the natural cycle controls, but the difference was not significant (11.8% vs 5.9%, P  > 0.05). Conclusion This study supported the hypothesis that P-primed minimal stimulation achieved ovulation control of the dominant follicle and did not adversely affect the quality of oocytes in poor responders. Therefore, P-priming is a promising approach to overcome premature ovulation in minimal stimulation for poor responders. Trial registration ChiCTR-OCH-14004176 . Registered on January 8, 2014.

Background Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. Methods This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. Results Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P  = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. Conclusion This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.

This study aimed to evaluate the effect of acupuncture treatment as an alternative therapy on ovulation rate, pregnancy rate, and endometrial receptivity in infertile patients with polycystic ovary syndrome (PCOS). This was a randomized, single-blind, sham acupuncture-controlled clinical trial that included 134 patients who met the inclusion criteria for PCOS infertility. Both groups received letrozole as the base treatment, with the treatment group receiving additional acupuncture treatment twice a week and the control group receiving placebo acupuncture treatment throughout three menstrual cycles. The study collected data collection at baseline, at the end of treatment, looking at ovulation rate, pregnancy rate, sex hormone levels [follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), prolactin (PRL)], endometrial receptivity (Salle Score), assessment of uterine using resistance index (RI), pulsatility index (PI) blood flow. The ovulation and pregnancy rate across treatment cycles of women in the treatment group were significantly higher than those in the control group (77.97 % and 49.74 % ovulation rate and 56.72 % and 29.85 % pregnancy rate across treatment cycles, respectively). Comparison of sex hormone levels showed a significant decrease in testosterone (T) levels in the treatment group (P = 0.005). In comparison of endometrial receptivity by Salle score, the total effective rate of the treatment group (86.4 %) was significantly higher than that of the control group (67.2 %), which was different between the two groups (P = 0.005). In comparison of PI and RI, the PI and RI of the treatment group were significantly lower than that of the control group (P < 0.001). Acupuncture treatment can effectively improve ovulation and pregnancy rate across treatment cycles, reduce androgens, and regulate endometrial receptivity in infertile patients with polycystic ovary syndrome, a finding that supports the use of acupuncture as an alternative therapy for treating infertile patients and provides a reference for individualized treatment strategies. •First RCT of acupuncture vs. sham acupuncture plus letrozole in PCOS-related infertility (n = 134).•Acupuncture doubled pregnancy rate (56.7 % vs. 29.9 %) and raised ovulation rate by 57 % during treatment.•Reduced testosterone (P = 0.005) and improved endometrial receptivity via Salle score (86.4 % vs. 67.2 %).•Improved uterine perfusion with lower PI/RI values (P < 0.001), supporting embryo implantation.•Acupuncture offers Class II evidence as a cost-effective adjuvant for PCOS infertility treatment.

PurposeTo compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency.MethodsSecondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18–40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable.ResultsAmong women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02).ConclusionsIn this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

Germ cells are physically coupled to somatic support cells of the gonad during differentiation, but this coupling must be disrupted when they are mature, freeing them to participate in fertilization. In mammalian females, coupling occurs via specialized filopodia that project from the ovarian follicular granulosa cells to the oocyte. Here, we show that signaling through the epidermal growth factor receptor (EGFR) in the granulosa, which becomes activated at ovulation, uncouples the germ and somatic cells by triggering a massive and temporally synchronized retraction of the filopodia. Although EGFR signaling triggers meiotic maturation of the oocyte, filopodial retraction is independent of the germ cell state, being regulated solely within the somatic compartment, where it requires ERK-dependent calpain-mediated loss of filopodia-oocyte adhesion followed by Arp2/3-mediated filopodial shortening. By uncovering the mechanism regulating germ-soma uncoupling at ovulation, our results open a path to improving oocyte quality in human and animal reproduction. Uncoupling of mature oocytes from somatic granulosa cells is required for their fertilization. Here the authors show that activation of EGFR signalling in granulosa cells during ovulation triggers ERK-dependent loss of filopodia oocyte adhesion, and Arp2/3 mediated retraction of granulosa cell filopodia.

Several studies have evaluated the reliability of using temperature sensors placed in different locations on the body to identify the day of ovulation. However, such demonstrations are lacking for axillary temperature wearable devices. This study aimed to evaluate the accuracy with which an axillary temperature armband sensor (Tempdrop) identifies the day of ovulation and the fertile window, using the Clearblue Connected Ovulation Test System as the reference method. A total of 194 cycles were analyzed from 125 women that participated in the study between April 2023 and June 2024. The performance parameters were high: the sensitivity (96.8% (95% CI 95.6; 97.7)), specificity (99.1% (98.8; 99.4)), accuracy (98.6% (98.2; 98.9)), positive predictive value (96.8% (95.6; 97.7)) and negative predictive value (99.1% (98.8; 99.4)). Furthermore, the results revealed a remarkably clear and better-than-expected change in temperature around the time of ovulation. This axillary temperature wearable sensor is an effective alternative to urine ovulation tests for determining the timing of ovulation. Another advantage is that it provides a clear temperature curve that can be used to evaluate the quality of the luteal phase.

Macrophages are the most abundant immune cells in the ovary. In addition to their roles in the innate immune system, these heterogeneous tissue-resident cells are responsive to tissue-derived signals, adapt to their local tissue environment, and specialize in unique functions to maintain tissue homeostasis. Research in the past decades has established a strong link between macrophages and various aspects of ovarian physiology, indicating a pivotal role of macrophages in ovarian health. However, unlike other intensively studied organs, the knowledge of ovarian macrophages dates back to the time when the heterogeneity of ontogeny, phenotype, and function of macrophages was not fully understood. In this review, we discuss the evolving understanding of the biology of ovarian tissue-resident macrophages, highlight their regulatory roles in normal ovarian functions, review the association between certain ovarian pathologies and disturbed macrophage homeostasis, and finally, discuss the technologies that are essential for addressing key questions in the field. Summary sentence Macrophages exhibit different origins, heterogeneous phenotypes and activation states, and are actively involved in multiple aspects of ovarian physiology and pathologies.

Abstract The mammalian target of rapamycin (mTOR) signaling pathway is activated by luteinizing hormone in preovulatory follicle. However, its impact on ovulation remains inadequately explored. Utilizing in vivo studies and in vitro fertilization, we demonstrated that the negative effect of inhibition of mTOR signaling by rapamycin on oocyte quality during the ovulatory phase, with a notable decrease in the total cell count of blastocysts, a reduction in gastrula size, and fetal degeneration on the 16th day of gestation while not affecting ovulated oocyte count or granulosa cell luteinization. Mechanistically, our study elucidated that in the ovulatory phase, mTOR signaling inhibition enhances lipid consumption, mitochondrial membrane potential of oocytes, and ATP generation. As a result, embryos derived from these oocytes exhibit higher levels of reactive oxygen species, insufficient energy supply, and lower developmental potency. Furthermore, the impact of mTOR signaling on oocytes remains consistent across various species, and its inhibition has been demonstrated to enhance energy metabolism during the in vitro maturation process of bovine oocytes. These findings demonstrate the critical role of mTOR signaling during the ovulatory phase in balancing oocyte energy metabolism, enriching our understanding of the role of mTOR on ovulation regulation. The mTOR pathway maintains energy metabolism balance in oocytes during the ovulatory phase. Its disruption elevates metabolism and lipid consumption, ultimately yielding poor-quality oocytes. Graphical Abstract Graphical Abstract

Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen's current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers. Extensive past clinical experience with transgender women's CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women's literature to assess current therapy and clinical outcomes, including morbidity and mortality. To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women's CHT. It is important to add progesterone to estradiol and an antiandrogen in transgender women's CHT. Progesterone may add the following: (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits. Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.

Oura Ring is a wearable device that estimates ovulation dates using physiology data recorded from the finger. Estimating the ovulation date can aid fertility management for conception or nonhormonal contraception and provides insights into follicular and luteal phase lengths. Across the reproductive lifespan, changes in these phase lengths can serve as a biomarker for reproductive health. We assessed the strengths, weaknesses, and limitations of using physiology from the Oura Ring to estimate the ovulation date. We compared performance across cycle length, cycle variability, and participant age. In each subgroup, we compared the algorithm's performance with the traditional calendar method, which estimates the ovulation date based on an individual's last period start date and average menstrual cycle length. The study sample contained 1155 ovulatory menstrual cycles from 964 participants recruited from the Oura Ring commercial database. Ovulation prediction kits served as a benchmark to evaluate the performance. The Fisher test was used to determine an odds ratio to assess if ovulation detection rate significantly differed between methods or subgroups. The Mann-Whitney U test was used to determine if the accuracy of the estimated ovulation date differed between the estimated and reference ovulation dates. The physiology method detected 1113 (96.4%) of 1155 ovulations with an average error of 1.26 days, which was significantly lower (U=904942.0, P<.001) than the calendar method's average error of 3.44 days. The physiology method had significantly better accuracy across all cycle lengths, cycle variability groups, and age groups compared with the calendar method (P<.001). The physiology method detected fewer ovulations in short cycles (odds ratio 3.56, 95% CI 1.65-8.06; P=.008) but did not differ between typical and long or abnormally long cycles. Abnormally long cycle lengths were associated with decreased accuracy (U=22,383, P=.03), with a mean absolute error of 1.7 (SEM .09) days compared with 1.18 (SEM .02) days. The physiology method was not associated with differences in accuracy across age or typical cycle variability, while the calendar method performed significantly worse in participants with irregular cycles (U=21,643, P<.001). The physiology method demonstrated superior accuracy over the calendar method, with approximately 3-fold improvement. Calendar-based fertility tracking could be used as a backup in cases of insufficient physiology data but should be used with caution, particularly for individuals with irregular menstrual cycles. Our analyses suggest the physiology method can reliably estimate ovulation dates for adults aged 18-52 years, across a variety of cycle lengths, and in users with regular or irregular cycles. This method may be used as a tool to improve fertile window estimation, which can aid in conceiving or preventing pregnancies. This method also offers a low-effort solution for follicular and luteal phase length tracking, which are key biomarkers for reproductive health.