Luteal Phase Defect Research Articles

Current Ovulation and Luteal Phase Tracking Methods and Technologies for Fertility and Family Planning: A Review

AbstractOvulation is critical for both conception and overall health, but many people who may ovulate are not tracking ovulation or any other part of their menstrual cycle. Failure to track ovulation, especially in those trying to conceive, can lead to fertility challenges due to absent ovulation, mistiming intercourse, or an undetected luteal phase defect. Ovulatory disorders and mistiming intercourse are both primary causes of infertility, and tracking ovulation is shown to decrease the average time to conception. While there are many tracking methods and apps available, the majority are predictive apps or ovulation predictor kits and do not test or track both successful ovulation and the health of the luteal phase, leading to missing information that could contribute to diagnosis or successful conception. Here, we review why ovulation tracking and a healthy luteal phase are important for those trying to conceive. We present currently available ovulation tracking methods that detect both ovulation and the luteal phase, including cervical mucus, urinary hormone testing, and basal body temperature, and discuss the use, advantages, and disadvantages of each. Finally, we consider the role of digital applications and tracking technologies in ovulation tracking.

Luteal Phase Defects and Progesterone Supplementation

Importance: Luteal phase defects (LPDs), or an insufficiency of progesterone production during the luteal phase of the menstrual cycle, have been identified as a potential cause of recurrent pregnancy loss (RPL), but its exact contribution to RPL is not well-defined. In addition, the role of exogenous progesterone supplementation during pregnancy remains controversial. Objective: The goal of this review is to provide an updated, evidence-based summary of LPD, including prevalence and potential pathophysiologic mechanisms, and to explore the current controversies regarding progesterone supplementation for management and treatment of RPL. Evidence Acquisition: A literature review identified relevant research using a PubMed search, Cochrane summaries, review articles, textbook chapters, databases, and society guidelines. Results: Endogenous progesterone plays a crucial role in the first trimester of pregnancy, and therefore, insufficiency may contribute to RPL. However, the precise relationship between LPD and RPL remains unclear. LPD is primarily a clinical diagnosis based on a luteal phase less than 10 days. Although there may be a possibility of incorporating a combined clinical and biochemical approach in defining LPD, the current lack of validated diagnostic criteria creates a challenge for its routine incorporation in the workup of infertility. Moreover, no treatment modality has demonstrated efficacy in improving fertility outcomes for LPD patients, including progesterone supplementation, whose inconsistent data do not sufficiently support its routine use, despite its minimal risk. It is imperative that women diagnosed with LPD should be worked up for other potential conditions that may contribute to a shortened luteal phase. Future work needs to focus on identifying a reproducible diagnostic test for LPD to guide treatment. Conclusions and Relevance: Currently, the perceived relationship between LPD and RPL is challenged by conflicting data. Therefore, patients with an abnormal luteal phase should undergo a thorough workup to address any other potential etiologies. Although supplemental progesterone is commonly used for treatment of LPD and RPL, inconsistent supporting data call for exogenous hormone therapy to be only used in a research setting or after a thorough discussion of its shortcomings.

Luteal Phase Defects and Progesterone Supplementation

Luteal Phase Defects and Progesterone Supplementation

An Ayurvedic Approach on Recurrent Pregnancy Loss due to Luteal Phase Defect W.S.R to Putraghni Yoni Vyapad: A Case Study

An Ayurvedic Approach on Recurrent Pregnancy Loss due to Luteal Phase Defect W.S.R to Putraghni Yoni Vyapad: A Case Study

Hotspots and frontiers in luteal phase defect research: An in-depth global trend bibliometric and visualization analysis over a 52-year period

Luteal phase defect (LPD) is a common female reproductive endocrine defect，which is associated not only with certain diseases but also with the menstrual cycle and fertility in women. With the development of assisted reproductive technology (ART) in recent years, the incidence of luteal phase defect is high among patients using assisted reproductive technology. The aim of this study was to evaluate worldwide research on luteal phase defects using bibliometric analysis. A total of 631 documents related to the study of luteal phase defect were identified over the last 52 years. The current status and trend of globalization can be comprehended by analyzing the annual number of publications, institutions, authors, countries and regions of corresponding authors, journals, influential luteal phase defect publications (which were highly cited), highly cited references in luteal phase defect publications (cocitation analysis) and keywords. The study results provide a comprehensive overview of the development of scientific literature and are of great significance for the future development of the field，especially infertility and early pregnancy loss.

P-449 Association of corpus luteum activity in early pregnancy and live birth after assisted reproductive technology (ART) and intrauterine insemination (IUI)

Abstract Study question What is the incidence of low corpus luteum activity in early pregnancy, and how are endogenous progesterone levels and live birth achievement associated? Summary answer Frequently occurring low corpus luteum activity (progesterone-level) in early pregnancy after ART and IUI strongly predicts pregnancy demise, though not independent of trophoblast activity (hCG-level). What is known already Ovarian stimulation and human chorion gonadotropine (hCG) administration may induce a luteal phase defect via negative feedback on the hypothalamic-pituitary-ovarian (HPO) axis. Luteal phase support (LPS) is routinely administered with bio-identical progesterone or oral dydrogesterone (DYD). DYD has high oral availability, minimal interaction with the pituitary gland, and no cross-reactivity in enzyme-linked immunosorbent assay (ELISA) with progesterone. Therefore, utilizing DYD as LPS in IVF/ICSI or ovulatory IUI cycles provides a unique perspective to assess endocrine luteal activity. While various studies explored progesterone and hCG post-IVF or IUI, none focused solely on the corpus luteum’s sole endocrine function and its outcomes. Study design, size, duration This single-center, retrospective study (with institutional review board approval) investigated hCG and progesterone serum levels after IVF/ICSI cycles or IUI cycles supported with DYD as the sole LPS. The study aims to assess their predictive value, individually and in combination, for sustaining pregnancy. Data from 189 IVF/ICSI and 198 IUI early pregnancies, respectively, with positive hCG test between January 2017 and June 2022, was extracted from the patient management system at the University Fertility Center. Participants/materials, setting, methods Included were only first IVF/ICSI and IUI treatment-cycles with serum hCG value ≥ limit of detection (0.6 IU/l) between days 9 and 16 after fresh embryo transfer or IUI, respectively. Additionally to hCG, endogenous progesterone was determined and the relationship between these and pregnancy maintenance was investigated using logistic regression analysis. Inclusion criteria encompassed hCG-triggered cycles using DYD as the sole LPS, administered at 30 and 20 mg daily for IVF/ICSI and IUI therapy, respectively. Main results and the role of chance The 10th, 25th, 50th and 75th quantiles of serum progesterone are at 0.28, 3.75, 33.0 and 98.7 µg/l in IVF/ICSI cycles and 0.48, 2.70, 18.40 and 26.6 µg/l in IUI cycles. Women in the first quartile of progesterone levels had nearly exclusively pregnancy demise: live birth rate 3/47 (7%, 95% confidence interval (CI) 1-19%) and 0/47 (0%, 95% CI 0-7.5%) in IVF/ICSI and IUI cycles, respectively. In both IVF/ICSI and IUI, progesterone and hCG were highly correlated (correlation coefficient 0.83 in both cases). Accordingly, the association of serum hCG levels with live birth achievement was similar in quartile analyses. Using receiver operating characteristic (ROC) curves and Youden’s indices, the optimal cut-off values for predicting live birth were determined as follows: 16.49 µg/l (89 % sensitivity (SN) and 59 % specificity (SP)) for IVF/ICSI and 15.89 µg/l (90 % SN and 70 % SP) for IUI therapy. Logarithmic regression analysis also revealed a significant correlation between progesterone levels and live birth in IVF/ICSI and IUI therapy, with a p-value of < 0.001. Limitations, reasons for caution Low progesterone in early pregnancy may be a consequence or a cause for pregnancy demise. DYD, like any other progesterone for LPS, might adversely impact corpus luteum formation and maintenance through HPO axis interaction, especially in mono-ovulatory cycles or in older women with inherently higher risk of luteal phase defect. Wider implications of the findings Ovarian stimulation and hCG-administration may induce a luteal phase defect with insufficient luteal activity in early pregnancy, even up to luteolysis, with potential consequences for pregnancy maintenance and maternal/fetal health. Future treatment protocols may require exploring an optimal luteotropic state at pregnancy’s outset, necessitating the establishment of relevant markers. Trial registration number not applicable

Impact of a hypocaloric dietary intervention on antral follicle dynamics in eumenorrheic women with obesity.

Do antral follicle dynamics change in women with obesity and regular ovulatory cycles after a 6-month hypocaloric dietary intervention? After a 6-month hypocaloric dietary intervention, women with obesity and regular ovulatory cycles displayed evidence of improved antral follicle dynamics defined by the emergence of more dominant follicles, larger ovulatory follicle diameter at selection, and increased luteal progesterone concentrations compared to pre-intervention. Precise events in antral folliculogenesis must occur in order for natural and regular monthly ovulation. In healthy women of reproductive age, antral follicles are recruited for growth in a wave-like fashion, wherein a subset of follicles are selected for preferential growth, and typically, one dominant follicle culminates in ovulation. Women with obesity and regular ovulatory cycles display evidence of suppressed antral follicle development, as evidenced by fewer recruitment events, fewer selectable and dominant follicles, smaller diameter of the ovulatory follicle at selection, and a higher prevalence of luteal phase defects. While improvements in gonadotropin and ovarian steroid hormone concentrations after weight loss have been documented in eumenorrheic women with obesity, the precise impact of weight loss on antral follicle dynamics has not been evaluated. A pre-post pilot study of 12 women who participated in a 6-month hypocaloric dietary intervention. Twelve women with obesity (total body fat ≥35%) underwent transvaginal ultrasonography and venipuncture every-other-day for one inter-ovulatory interval (IOI) both before (baseline) and during the final month (Month 7) of a six-month hypocaloric dietary intervention. Participants were aged 24-34 years and had a self-reported history of regular menstrual cycles (25-35 days). Follicle number and diameter (≥2 mm) were quantified at each study visit, and individual growth profiles for all follicles ≥7 mm were determined. Blood samples were assayed for reproductive hormones. Follicle dynamics and reproductive hormone concentrations were compared pre- and post-intervention. Further, post-intervention follicle and endocrine dynamics (Month 7 IOI) were compared to an age-matched reference cohort of lean women with regular ovulatory cycles (total body fat <35%, N = 21). Participants lost an average of 11% of their original body weight with the hypocaloric dietary intervention. More dominant follicles were detected (≥10 mm) at Month 7 compared to baseline (0. 3 ± 0.4 versus 0.4 ± 0.5 follicles, P = 0.001), and ovulatory follicles were selected at larger diameters post-intervention (7.3 ± 2.0 versus 10.9 ± 2.6 mm, P = 0.007). Luteal progesterone concentrations were increased at Month 7 compared to baseline (5.3 ± 3.65 versus 6.3 ± 4.74 ng/ml, P < 0.0001). However, risk for luteal phase dysfunction as judged by the prevalence of a luteal phase length <10 days, integrated luteal progesterone levels <80 ng/ml or peak progesterone <10 ng/ml did not differ pre- versus post-intervention (all, P > 0.05). In Month 7, follicle dynamics and endocrine profiles were similar to the reference cohort across all measures. This study does not inform on the earliest stages of ovarian follicle development and is limited to providing knowledge on the later stages of antral follicle development. This study cannot fully address causation between weight loss and sustained improvements in antral follicle dynamics. The data cannot be extrapolated to comment on potential improvements in fertility and fecundity with weight loss. The small group sizes limit statistical power. The increasing prevalence of obesity necessitates an understanding of the mechanisms that underlie potential improvements in reproductive health outcomes with weight loss. Women with obesity and regular ovulatory cycles who undertook a 6-month hypocaloric dietary intervention demonstrated improvements consistent with benefits of lifestyle intervention on reproductive health even in those without overt signs of reproductive dysfunction. Potential improvements in the cellular makeup of follicles, which may underlie the restoration of normal follicle development and amelioration of subfertility, require further investigation. Cornell University, President's Council of Cornell Women, United States Department of Agriculture (Grant No. 8106), and National Institutes of Health (R01-HD0937848). B.Y.J. and H.V.B. were supported by doctoral training awards from the National Institutes of Health (T32-DK007158) and Canadian Institutes of Health Research (Grant No. 146182), respectively. The authors have no competing interests. NCT01927432 and NCT01785719.

Are menstrual disturbances associated with an energy availability threshold? A critical review of the evidence.

Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a threshold of energy availability (EA) of 30kcal/kg lean body mass (LBM)/day. This paper is a critical review of the evidence regarding the theory that disruptions to the reproductive axis and menstrual disturbances occur below the proposed threshold. Short-term laboratory studies demonstrated that 4-5 days of an EA below 30kcal/kg LBM/day, induced with or without exercise, decreased serum triiodothyronine and LH pulse frequency, and increased LH pulse amplitude in sedentary, regularly menstruating women. Fewer studies have investigated downstream ovarian effects after long-term exposure to low EA. The Sargent Camp Study was the first randomized trial that induced luteal phase defects, delayed menses, and anovulation by causing weight loss (-4± 0.3kg) with an abrupt increase in exercise volume for two menstrual cycles. The BioEnergetics Study was a randomized controlled trial that induced varying levels of energy deficits by manipulating energy intake and expenditure for three menstrual cycles. LH pulse frequency and triiodothyronine decreased, and 57% of women developed luteal phase defects, anovulation, and/or oligomenorrhea. An EA below 30kcal/kg fat free mass/day increased the chance of experiencing a menstrual disturbance by 50%. However, menstrual disturbances were observed above and below that EA threshold, and changes in LH pulse frequency predicted only luteal phase defects, not oligomenorrhea or anovulation. The proposed EA threshold is not a cut-off below which menstrual disturbances occur, but represents an increased risk of experiencing menstrual disturbances.

#369 : A Case of Luteal Phase Deficiency (LPD) and Polycystic Ovarian Syndrome (PCOS). When Routine is not Enough

Background and Aims: Luteal phase deficiency (LPD) is a consequence of the inability of the corpus luteum (CL) to produce an adequate level of progesterone. This manifests clinically as a short menstrual cycle and infertility. Abnormal follicular development and inadequate steroidogenesis in lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and PCOS are independent disorders sharing a common pathophysiology. The aim of this case report is to highlight the importance of additional luteal phase support for patients with PCOS. Case report: A 34-year-old Indian lady with anovulation secondary to PCOS failed to get pregnant after 7 years of marriage. Her menses were irregular, and she had hirsutism. She was also overweight. (BMI 26.4 kg/m2) Her hormonal profile showed a reversal of the FSH/LH ratio of 2:1, and serum progesterone was low. (&lt;1.6 IU/L). A transvaginal scan showed a classic pearl string sign, which was typical for patients with PCOS. She underwent laparoscopic dye insufflation and ovarian drilling, during which four puncture points were made on each ovary at 4 watts for 4 seconds. Later, she underwent a round of timed sexual intercourse and intrauterine insemination. (IUI) Dydrogesterone (10 mg, 8 hourly) was started for luteal phase support as per unit protocol. However, she complained of per vaginal spotting starting on day 7 after human chorionic gonadotropin (hcg) trigger, and both times, treatment was unsuccessful. Then, she had another round of ovarian stimulation with clomiphene citrate 50 mg daily and had IUI. She was given micronized progesterone 100 mg 12 hours a day in addition to the dydrogesterone. The urine pregnancy test was positive, and she is having a healthy, on-going pregnancy. Conclusion: Patients with PCOS may suffer from a defective luteal phase. Hence, it is important to supplement PCOS patients with additional support during the luteal phase, as this can lead to a successful pregnancy.

The Role of Dydrogesterone in the Management of Luteal Phase Defect: A Comprehensive Review.

The luteal phase of the menstrual cycle is a pivotal period characterized by hormonal intricacies that lay the foundation for successful embryo implantation and early pregnancy development. Luteal phase defect (LPD), marked by abnormalities in luteal function, presents challenges that can impede reproductive outcomes. This comprehensive review article explores the role of dydrogesterone in LPD management, elucidating its mechanisms of action, evidence of efficacy, safety profile, and potential in combination therapies. Dydrogesterone, a synthetic progestogen, closely mirrors natural progesterone's actions, effectively supplementing the luteal phase and enhancing endometrial receptivity. Clinical studies demonstrate improved pregnancy rates, extended luteal phase support, and enhanced reproductive outcomes with dydrogesterone supplementation. Its favorable safety profile, minimal side effects, and reduced risk of unwanted hormonal effects contribute to its appeal. Furthermore, dydrogesterone's inclusion in international guidelines solidifies its importance in LPD management. Combination therapies, leveraging synergistic effects, offer a comprehensive approach. As gaps in knowledge persist, future research directions and personalized treatment strategies pave the way for a future where dydrogesterone stands as a beacon of hope in conquering the challenges of LPD and achieving successful reproductive outcomes.

P-652 RCT to evaluate the necessity of routine luteal phase support after ovarian stimulation by oral ovulogens in intrauterine insemination (IUI) cycles

Abstract Study question 1. Is it beneficial to provide luteal phase support in each IUI cycle stimulated by oral ovulogens ? Summary answer 1. Luteal phase support with progesterone makes no significant difference in clinical pregnancy rate in oral ovulogen stimulated IUI cycles. What is known already ART (assisted reproductive techniques) involves superovulation to achieve the development of multiple follicles. This produces supraphysiological E2 levels that causes feedback inhibition of FSH and LH in luteal phase leading to luteal phase defect. In IUI,only few follicles develop ,so the above phenomenon is rarely seen. Today widespread use of progesterone in clinical practice has become a habit, instead of the need, adding to burden of medication and cost to the patient without much evidence to recommend it. Study design, size, duration Prospective Randomized control over 1 year 200 IUI cycles randomized to either supplementing luteal phase with tab dydrogesterone (Group A ,no.100) or not supplementing (Group B, No. 100) as per inclusion(Unexplained infertility,Mild male factor,Donor sperm IUI, PCOD,Coital factors,Mild endometriosis) and exclusion criteria(IUI with gonatotropin, age more than 38 years, thin endometrium ,previous two or more IUI failures, history suggestive of luteal phase defect, recurrent pregnancy loss, structural uterine anomaly, history of endocrine or autoimmune diseases) Participants/materials, setting, methods Transvaginal scan was conducted on day 2 , followed by ovarian stimulation with letrozole 2.5 mg for 5 days. HCG trigger (10000IU) was given When follicle reached 18- 24mm with endometrium &amp;gt;7mm and IUI timed 36 hours after. Computer generated random allocation was done with one group receiving luteal phase support with tab dydrogesterone 10mg twice a day(Group A)and other not receiving LPS(Group B).Outcome of study was studied in terms of clinical pregnancy on USG. Main results and the role of chance Among the patients recruited, infertility was observed to be primary infertility in 74% cases in Group B and 72% in Group A , whereas secondary infertility was observed in 26% cases in group B and 28% in group A (P = 0.75). Group B included mild male factor in 29%, 24% of polycystic ovarian syndrome, 17 % tubal, 15% poor ovarian reserve, 9% of unexplained and 6% had endometriosis. Whereas in group A, PCOS (25%),male factor (21%),poor ovarian reserve and unexplained in 20%, endometriosis in 8% and 6% had tubal infertility. Among patients, mean endometrium thickness on trigger day of group Band group A were 8.46 ± 1.36mm and 8.44 ± 1.17mm respectively. Conception was reported by a positive urine pregnancy test . Among Group B , 23% had a positive urine pregnancy test. Whereas, in controls Group A 21% had a positive test, the difference being statistically non-significant (p value = 0.733) Outcomes were expressed terms of clinical pregnancy described as the presence of intrauterine sac with foetal heart rate. Clinical pregnancy rate was 22% of group B and 21% in group A , difference was statistically nonsignificant (p = 0.755). Limitations, reasons for caution Due to limited period of study and hence restricted sample size, the trial needs to be extended over a larger sample size for further interpretation. Further subgroup analysis needs to be conducted when a larger study group is recruited. Wider implications of the findings This study suggested that luteal support does not significantly affect the clinical pregnancy rate in IUI cycles with oral ovulogens .Our study could be a basis for further analysis to determine whether treatment burden in the form of luteal phase support can be reduced in such patients. Trial registration number not applicable

Ovarian stimulation methods at a single-assisted reproductive technology institution: a retrospective study of successful outcomes

Aim : to examine an efficacy of various stimulation methods in a group of successful pregnancies. Materials and Methods . In a single center retrospective study 47 pregnancy cases were examined after performing embryo transfers at our institution from the years 2017 to 2021. Patients were divided into four groups: i) clomiphene hyperstimulation (CH), ii) stimulation with gonadotropin-releasing hormone (GnRH) agonist, iii) with GnRH antagonist, and iv) progestin-primed ovarian stimulation (PPOS). Age, anti-Mullerian hormone, presence of chronic disease, number of in-vitro fertilizations prior to conception, dosage of follicle stimulating hormone (FSH), presence of premature luteinizing hormone surge, number of egg retrievals, fertilization rate, and live birth rate were assessed. Results. The number of pregnancies obtained by CH, agonist, antagonist, and PPOS methods comprised 25, 12, 2, and 8 cases, respectively. No significant difference in parameters between CH group and non-CH groups, excepting FSH was observed. The FSH was used in CH group and non-CH group at dose of 1108 ± 468 IU and 1756 ± 394 IU, respectively (p &lt; 0.0001). Conclusion. CH is not commonly used due to potential luteal phase defects, but it is thought to be cost-effective, requiring lower FSH doses, requiring no ovulation suppression antagonists, and exerting no effect on frozen embryos or fetuses. Hence, CH could be a suitable protocol for egg retrieval in Japan.

Using GnRH agonists in combination with hCG in antagonist ART cycles: A SCOPING Review of recent evidences.

Assisted Reproductive technology encompasses all techniques involving ovarian stimulation to produce high-quality oocytes and manipulation of both oocytes and sperm in vitro to produce embryos for the purpose of reproduction. The final maturation of oocytes induced by a "trigger" is a crucial step with the potential to affect in vitro fertilization outcomes. Human chorionic gonadotropin has traditionally been used as a substitute for luteinizing hormone to induce final oocyte maturation and meiosis. However, this practice may cause a potentially fatal iatrogenic complication known as ovarian hyperstimulation syndrome, which can cause significant morbidity and, in rare cases, death in otherwise healthy women. Thus, gonadotropin releasing hormone agonists have been promoted as a safer alternative for inducing oocyte maturation, albeit at the expense of luteal phase defect. Since then, various combinations of gonadotropin releasing hormone agonists and human chorionic gonadotropin have been tried. This scoping review evaluates these trigger combinations in various types of responders.

Female Athlete Triad Recognition and Knowledge of Collegiate Cross-country Coaches

The Female Athlete Triad (Triad) refers to the triad of low energy availability, impaired menstrual function and low bone density. However each component of the Triad is, in fact, a spectrum with energy availability ranging from normal to low, menstrual function ranging from normal to luteal phase defects and anovulatory cycles to frank functional hypothalamic amenorrhea (FHA, absence of menses) and bone density ranging from normal to low. There is obviously a need to engage coaches in education efforts so they know about the Triad and its components, can pass on this information to their teams, be comfortable discussing dietetic and menstrual issues with female athletes, and recognize Triad symptoms early and bring these to medical attention in a timely fashion. Coaches are in a unique position to educate athletes and prevent the Triad from developing or worsening over time, and to advocate for optimal resources including for the services of a sports dietician and psychologist.

Continuous light exposure influences luteinization and luteal function of ovary in ICR mice.

With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD). We used continuous light-exposed mice as a model to observe whether continuous light exposure may affect luteinization and luteal function. We showed that the level of progesterone in serum reduced (p < .001), the number of corpus luteum (CL) decreased (p < .01), and the expressions of luteinization-related genes (Lhcgr, Star, Ptgfr, and Runx2), clock genes (Clock and Per1), and Mt1 were downregulated (p < .05) in the ovaries of mice exposed to continuous light, suggesting that continuous light exposure induces defects in luteinization and luteal functions. Strikingly, injection of melatonin (3 mg/kg) could improve luteal functions in continuous light-exposed mice. Moreover, we found that, after 2 h of hCG injection, the level of pERK1/2 in the ovary decreased in the continuous light group, but increased in the melatonin administration group, suggesting that melatonin can improve LPD caused by continuous light exposure through activating the ERK1/2 pathway. In summary, our data demonstrate that continuous light exposure affects ovary luteinization and luteal function, which can be rescued by melatonin.

Neuroendocrine Blockade of the Reproductive Axis in Female Athletes

This review aims at defining the neuroendocrine mechanisms underlying the sport-induced restrictions of the reproductive axis in female athletes. Episodic gonadotropin release was found to be compromised, presumably a result of impaired hypothalamic pulsatile GnRH release. Any deviation from optimal gonadotropin release may result in a suboptimal function of the ovaries, leading to disorders of the menstrual cycle and ovulation. A whole spectrum of menstrual dysfunctions ranging from ovulatory eumenorrhea to luteal phase defects and amenorrhea has been reported in sportive women. As essential neuroendocrine factors underlying these observations, activation of the adrenal axis and altered central nervous neurotransmitter activity have been identified to transfer metabolic, nutritional, and stress signals into the hypothalamic GnRH release. The degree by which the neuroendocrine axis governing reproduction is impaired critically depends on the intensity and duration of exercise and the state of training. Other decisive factors may be energy expenditure and availability, nutritional components, and the maturity of the hypothalamic-pituitary-ovarian (HPO) axis when sport activity was initiated. In conclusion, the gradual cessation of reproductive function observed in female athletes may be interpreted as an adaptive mechanism in response to physical and psychological endurance during sport. This sport-induced restriction of reproductive capacity may serve as protection (endogenous contraception) to preserve a woman’s health.

OR06-4 Women With Obesity Display Defects in Follicular Recruitment, Selection, and Dominance Alongside Luteal Phase Dysfunction During Natural Ovulatory Cycles

Abstract Although obesity is closely associated with reproductive dysfunction, many women with obesity remain eumenorrheic. The degree to which obesity affects menstrual cycle characteristics in this population is limited to endocrine assessments with few data available on how endocrine aberrations align with defects in antral follicle development.We have previously shown alterations in the distribution of recruitable (2-5mm) versus selectable (6-9mm) follicles in those with obesity that were associated with decreased gonadotropin and progesterone production despite normal menstrual cycle length. The objectives of the present study were to further contrast follicular growth and endocrine dynamics between obese and non-obese eumenorrheic women with the goal of determining any alterations in distinct events in folliculogenesis. 21 non-obese (total percent body fat &amp;lt;35%) and 21 obese (total percent body fat ≥35%) reproductive age females with regular menstrual cycles (21-35d) were evaluated by serial ovarian transvaginal ultrasonography and venipuncture every-other-day for one complete inter-ovulatory interval (IOI). The number and diameters of all follicles ≥2mm at each visit were documented offline using the Grid Method. Growth profiles of individual follicles which grew to ≥7mm were assessed using the Identity Method to characterize antral follicle recruitment, selection, and ovulation. Clinical, morphologic, and endocrine features were compared across groups using t-tests and mixed models. Women with obesity exhibited fewer recruitment events versus non-obese women (1±0.6 vs. 2±0.9; p=0.010). They also had fewer selectable follicles (4±3 vs. 8±6 follicles/participant, p=0.022) which grew faster but remained static longer and regressed slower (all growth rates, p&amp;lt;0.05) compared to their non-obese counterparts. Anti-Mullerian hormone levels were lower in the obese versus non-obese group (4.40±3.01 vs. 5.94±2.49ng/mL, p=0.023). Of the selectable follicles, fewer progressed to ≥10mm in the obese versus non-obese group (1±0.7 vs. 2±0.8 follicles, p=0.030) with ultimately fewer anovulatory follicles achieving dominance (0±0.7 vs. 1±0.9 follicle, p=0.029). Ovulatory follicles in the obese group were selected at smaller diameters (7.5±1.6 vs. 9.5±1.9mm, p=0.001) versus their non-obese counterparts. However, the kinetics of dominant follicle growth were similar between groups. Post-ovulation, progesterone concentrations across the luteal phase were lower in women with obesity (4.95±3.34 vs. 7.85±5.74ng/mL, p=0.001) and the prevalence of luteal phase defects (LPDs) higher versus non-obese women, defined by either integrated (76 vs. 29%, p=0.002) or maximum (71 vs. 24%, p=0.002) progesterone levels. Eumenorrheic women with obesity display evidence of suppressed follicle dynamics as evidenced by fewer recruitment events, selectable follicles, and anovulatory dominant follicles. LPDs are more prevalent in women with obesity during natural ovulatory cycles which may underlie subfertility in this population. A smaller size at selection suggests premature responsiveness to luteinizing hormone which may result in suboptimal luteinization. Further studies are needed to elucidate the degree to which these defects impact fertility and fecundity in our increasingly obese demographic. Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.

Live Delivery in a 46.5-Year-Old Woman in Overt Menopause by Restoring Follicular Sensitivity to Follicle Stimulating Hormone (FSH)

For almost 40 years, there have been several publications where ovulation induction has occurred by lowering elevated serum follicle stimulating hormone (FSH) to up-regulate down-regulated FSH receptors on granulosa theca cells thus restoring follicular sensitivity to endogenous gonadotropins resulting in live deliveries. The majority of case reports used ethinyl estradiol to lower FSH. The advantage of ethinyl estradiol is that it does not add to the serum estradiol and thus allows the physician to better determine follicular maturation. To date the oldest woman to have ovulation induction and live delivery despite menopause was aged 45. A 46.5-year-old woman with 9 months of amenorrhea with a serum estradiol &lt;15 pg/mL and a serum FSH of 117 mIU/mL was given ethinyl estradiol 20 micrograms daily. She attained a mature follicle on day 44 and conceived with natural intercourse with vaginal progesterone supplementation in the luteal phase. She delivered a full-term healthy chromosomally normal baby. Interestingly, she also had a successful live delivery when we treated her with progesterone in the luteal phase at age 42 when her day 3 serum FSH was 47 mIU/mL. Besides a luteal phase defect, she failed to release the egg from the follicle first naturally then with 10,000 units of human chorionic gonadotropin (hCG) but finally did release and conceived with the novel use of granulocyte colony stimulating factor, which was used again at age 46.5. Live deliveries are uncommon in women aged 46 even with regular menses and normal egg reserve. Precedents are important in medicine. Thus, this case represents the oldest woman with documented menopause to conceive naturally.

The reproductive endocrine feature and conception outcome of women with unknown etiological menstrual cycle (36–45 days) with long follicular phase

Objective To explore the reproductive endocrine feature and conception outcome of women with unknown etiological long menstrual cycle (LMC) (36–45 days) with long follicular phase. Methods In the cohort study, we included 80 women with unknown etiological long menstrual cycle of biphasic basal body temperature (BBT) lasting for 36–45 days and 87 controls with normal cycle of biphasic BBT into LMC group and NMC group, respectively. Serum hormone levels, fasting glucose, and insulin of participants were tested, and ovulation was observed by ultrasound. The conception outcome was followed up within 12 menstrual cycles. Results In the LMC group, the rate of abnormality of HOMA-insulin resistance index (40.0% vs. 20.7%, p < .01), luteal phase defect (30.9% vs. 13.8%, p < .05) and abnormality of FSH/LH ratio (15.6% vs. 5.7%, p < .05) were all significantly higher, but the serum estradiol level on the day before ovulation (261.10 pg/mL vs. 320.26 pg/mL, p < .01) was lower. The rate of poor ovulation quality (31.3% vs.15.4%, p < .05) in the LMC group was significantly higher than the NMC group. In the LMC group, the natural conception rate within 12 menstrual cycles was lower (41.9% vs. 66.2%, p < .01), whereas the spontaneous abortion rate in early pregnancy (29.0% vs. 9.8%, p < .05) and the conversion rate (21.6% vs. 5.2%, p < .01) to anovulation within 12 cycles were significantly higher. Conclusions Women with unknown etiological menstrual cycle (36–45 days) with long follicular phase have greater endocrine abnormality and higher risk of spontaneous abortion, infertility, and conversion to anovulation. Moderate early intervention may be advisable for these women, especially those who wish to get pregnant.

Reproductive Outcome After GnRH Agonist Triggering With Co-Administration of 1500 IU hCG on the Day of Oocyte Retrieval in High Responders: A Long-Term Retrospective Cohort Study

While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients’ age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower.ConclusionThe results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.