Previous Menstrual Cycle Research Articles

Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.

What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window? Both oestrogen and progesterone contribute to a delay in the onset of the fertile window. Oestrogen enhances cervical mucus secretion while progesterone inhibits it. Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder. Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva. Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle. This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings. This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction. The authors declare no conflicts of interest. No funding was provided for this secondary data analysis. N/A.

Original Research The Effect of Yoga or Nonpharmacotherapy on Dysmenorrhore in Medical Students of Andalas University, Indonesia

Background: Dysmenorrhea is a menstrual pain that is often experienced by young women, with a global prevalence of 16.8-81%. In Indonesia, the prevalence reaches 54.89%, with adolescent girls being the largest group. Treatment generally uses analgesics, but it has side effects. Yoga as a non-pharmacological therapy can reduce pain through muscle relaxation. Purpose: Analyzing the effect of yoga therapy on the intensity of the degree of dysmenorrhea in female students of the Class of 2018 Undergraduate Medical Education Study Program, Faculty of Medicine, Andalas University. Methods: This research uses a pure experimental design with a pre-test, post-test, and only group design, with a sample size of 32 people. The research instrument used in the study was a pre-test and post-test questionnaire, which contained VAS scores and guidelines regarding yoga movements. The questionnaire contains a Visual Analog Scale (VAS), which consists of a vertical scale from 0 to 10 cm. Results: The results showed there were no differences related to age. As many as 18% of respondents usually took analgesics, while 81.3% did not take analgesics to treat dysmenorrhea before yoga therapy. Meanwhile, after yoga therapy, 5 out of 6 respondents who usually consumed analgesics in previous menstrual cycles no longer consumed analgesics, and one respondent still consumed analgesics. Bivariate analysis showed a value of p=0.00 (p<0.05), which means there is a relationship between the provision of yoga therapy and the degree of dysmenorrhea. Where providing yoga therapy can reduce the intensity of pain in respondents who experience dysmenorrhea. Conclusion: This research concludes that there is a significant relationship between the provision of yoga therapy and the degree of dysmenorrhea.

O-010 Luteal estradiol versus follicular GnRH antagonist for ovarian follicular synchronization in POSEIDON poor responders: a multicentric randomized controlled trial

Abstract Study question In order to improve follicular synchronization, is pre-treatment with Luteal Estradiol (LE) more efficacious than Follicular GnRH Antagonist (FA) among poor responders? Summary answer Luteal Estradiol is better than Follicular GnRH Antagonist to improve maturation rates in Poor Ovarian Responders (POR) What is known already In poor responders, follicular asynchrony is a major obstacle in optimizing the pregnancy rates and leads to more cycle cancellations and increases the requirement of additional pool up cycles. It imposes significant financial burden on patients. ESHRE recommendations on FA and LE are conditional and require better quality studies. Several studies have evaluated the individual role of pre-treatment with LE or FA in synchronising the number of mature oocytes retrieved. There have been no studies comparing the efficacy of luteal estradiol versus follicular antagonist Study design, size, duration A randomised controlled trial was conducted at multiple centres of a private fertility clinic over 1year. Block randomization was performed using a Web-based randomization system.Allocation concealment was done using envelopes. 196 POR patients were randomized and 145 successfully completed the study. 80 patients(55.17%) received LE while 65 patients (44.83%) received FA. A per-protocol analysis was conducted. A subgroup analyses was done after excluding endometriosis and male-factor infertility as they could have been significant confounding factors. Participants/materials, setting, methods We randomised POR patients(POSEIDON criteria) into 2 arms, in their previous menstrual cycle. LE arm received oral Estradiol valerate 4 mg/day from 7days before expected menses to Day1 of menses. FA arm received Inj.Cetrorelix 0.25mg S.C from Day1 to Day5 of menses. The primary outcomes analysed were oocytes retrieved ,Follicular Output Rate(FORT), Follicle-to-Oocyte Index(FOI), Ovarian Sensitivity Index(OSI), maturation rate and MII /AFC. Secondary outcomes were cycle cancellation rates, fertilization rate, cleavage rate and blastulation rate. Main results and the role of chance There was a significant improvement in maturation rates with luteal phase pre-treatment using estradiol (LE) compared to follicular GnRH antagonist (FA) (0.72 ± 0.03 vs. 0.63 ± 0.03, p-value = 0.045). However, there were no statistically significant differences observed in the oocytes retrieved, Follicle-to-Oocyte Index (FOI), Follicular Output Rate (FORT), or Ovarian Sensitivity Index (OSI) between the two pre-treatment groups. These non-significant differences remained consistent among both expected (poseidon category 3 and 4) and unexpected (posiedon group 1 and 2) poor responders. Secondary outcomes, including cycle cancellation rates, fertilization rate, cleavage rate, and blastulation rate, did not show significant variations between the luteal estradiol (LE) and follicular GnRH antagonist (FA) pre-treatment groups. Subgroup analyses without endometriosis (N = 136) and severe male factor infertility (N = 122), revealed no significant differences between the two study groups in these specific subpopulations. Limitations, reasons for caution Limited generalizability due to small sample size, potential bias from lack of blinding, restricted insight into long-term outcomes, and patient heterogeneity are notable limitations in this study. Wider implications of the findings Among poor responders, luteal estradiol demonstrated a significant improvement in maturation rates, probably due to better follicle synchronicity at trigger, compared to follicular antagonist. It’s also more cost-effective and patient-friendly. However, further research with larger sample size and long-term clinical endpoints are needed to validate these findings and optimise clinical strategies. Trial registration number CTRI registration no. CTRI/2023/06/053760

A formative investigation assessing menstrual health literacy in professional women’s football

ABSTRACTThe aim of this study was to assess and compare menstrual health literacy in professional women’s football. A three-section questionnaire was completed by professional players (n = 25), development players (n = 22) and staff (n = 19). The mean total knowledge score (out of 19) was lower for development players (5.4 ± 2.9) than professional players (7.8 ± 3.2) and staff (9.1 ± 4.8) (p < 0.001). No group achieved >50% correct answers. For each group, knowledge of the menstrual cycle (MC) was greater than knowledge of hormonal contraceptives (HC) (p < 0.001). Previous MC and HC education did not correspond to higher knowledge scores in professional players (p = 0.823) or development players (p = 0.274). In professional and development players, comfort of communication was influenced by the sex of whom they were communicating with (p < 0.001), with a preference for females. In conclusion, results from the present study suggest refined education strategies and new approaches are required for both players and staff to improve menstrual health literacy in professional women’s football.

Androgen and inhibin B levels during ovarian stimulation before and after 8 weeks of low-dose hCG priming in women with low ovarian reserve.

Does 8 weeks of daily low-dose hCG administration affect androgen or inhibin B levels in serum and/or follicular fluid (FF) during the subsequent IVF/ICSI cycle in women with low ovarian reserve? Androgen levels in serum and FF, and inhibin B levels in serum, decreased following 8 weeks of hCG administration. Recently, we showed that 8 weeks of low-dose hCG priming, in between two IVF/ICSI treatments in women with poor ovarian responder (anti-Müllerian hormone (AMH) <6.29 pmol/l), resulted in more follicles of 2-5 mm and less of 6-10-mm diameter at the start of stimulation and more retrieved oocytes at oocyte retrieval. The duration of stimulation and total FSH consumption was increased in the IVF/ICSI cycle after priming. Hypothetically, hCG priming stimulates intraovarian androgen synthesis causing upregulation of FSH receptors (FSHR) on granulosa cells. It was therefore unexpected that antral follicles were smaller and the stimulation time longer after hCG priming. This might indicate a different mechanism of action than previously suggested. Blood samples were drawn on stimulation day 1, stimulation days 5-6, trigger day, day of oocyte retrieval, and oocyte retrieval + 5 days in the IVF/ICSI cycles before and after hCG priming (the control and study cycles, respectively). FF was collected from the first aspirated follicle on both sides during oocyte retrieval in both cycles. The study was conducted as a prospective, paired, non-blinded, single-center study conducted between January 2021 and July 2021 at a tertiary care center. The 20 participants underwent two identical IVF/ICSI treatments: a control cycle including elective freezing of all blastocysts and a study cycle with fresh blastocyst transfer. The control and study cycles were separated by 8 weeks (two menstrual cycles) of hCG priming by daily injections of 260 IU recombinant hCG. Women aged 18-40 years with cycle lengths of 23-35 days and AMH <6.29 pmol/l were included. Control and study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol. Inhibin B was lower on stimulation day 1 after hCG priming (P = 0.05). Dehydroepiandrosterone sulfate (DHEAS) was significantly lower on stimulation day 1 (P = 0.03), and DHEAS and androstenedione were significantly lower on stimulation days 5-6 after priming (P = 0.02 and P = 0.02) The testosterone level in FF was significantly lower in the study cycle (P = 0.008), while the concentrations of inhibin B and androstenedione in the FF did not differ between the study and control cycles. A lower serum inhibin B in the study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the study cycle. This contradicts the theory that hCG priming increases the intraovarian androgen level, which in turn causes more FSHR on developing (antral up to preovulatory) follicles. However, based on this study, we cannot rule out that an increased intra-follicular androgen level was present at initiation of the ovarian stimulation, without elevating the androgen level in serum and that an increased androgen level may have rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. We retrieved significantly more oocytes in the Study cycle, and the production of estradiol per follicle ≥10-mm diameter on trigger day was comparable in the study and control cycles, suggesting that the rescued follicles were competent in terms of producing oocytes and steroid hormones. The sample size was small, and the study was not randomized. Our study design did not allow for the measurement and comparison of androgen levels or FSHR expression in small antral follicles before and immediately after the hCG-priming period. The results make us question the mechanism of action behind hCG priming prior to IVF. It is important to design a study with the puncture of small antral follicles before and immediately after priming to investigate the proposed hypothesis. Improved cycle outcomes, i.e. more retrieved oocytes, must be confirmed in a larger, preferably randomized study. This study was funded by an unrestricted grant from Gedeon Richter awarded to the institution. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co and payment for participation in an advisory board for Preglem. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S, and equipment and travel support has been given to the institution by Gedeon Richter Nordics AB. The remaining authors have no conflicts of interest to declare. ClinicalTrials.gov Identifier: NCT04643925.

P-682 Androgen and Inhibin B levels during ovarian stimulation before and after eight weeks of low dose hCG priming in women with low ovarian reserve

Abstract Study question Does eight weeks of low dose human chorionic gonadotropin (hCG)-priming affect androgen or Inhibin B levels in serum and follicular fluid during IVF/ICSI treatment? Summary answer Inhibin B was reduced on stimulation day 1 in the IVF/ICSI cycle following hCG-priming. Androgen levels in serum and follicular fluid was not increased. What is known already In our recently published pilot study, eight weeks of low-dose hCG-priming was used to stimulate the intraovarian androgen synthesis in women with AMH &amp;lt;6.29 pmol/L. Priming resulted in more retrieved oocytes and more follicles sized 2-5 mm and less sized 6-10 mm at the start of stimulation. Stimulation time and FSH consumption was increased after priming. HCG priming potentially stimulate the intraovarian androgen synthesis causing upregulation of FSH receptors on granulosa cells, and therefore it was unexpected that the antral follicles were smaller and stimulation time longer following priming. This might indicate a different mechanism of action than previously thought. Study design, size, duration A prospective, paired, non-blinded, single-center study including 20 women conducted between January 2021 and July 2021 at a tertiary referral hospital. Participants underwent two identical IVF treatments: a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycles were separated by eight weeks (two menstrual cycles) of hCG-priming by daily injections of 260 IE hCG (details in our previously published paper). Participants/materials, setting, methods Women aged 18-40 years with cycle lengths of 23-35 days and AMH &amp;lt;6.29 pmol/L. Control and Study IVF cycles were performed in a fixed GnRH-antagonist protocol. Blood samples were taken on stimulation day 1, stimulation day 5-6, trigger day, day of oocyte pick up (OPU), and trigger day + 7 days in the Control and Study cycles. Follicular fluid was collected from the first aspirated follicle on both sides during OPU in both cycles. Main results and the role of chance Inhibin B serum levels were significantly lower on stimulation day 1 after hCG-priming, but no other significant differences in serum Inhibin B or androgen levels were seen. The concentrations of Inhibin B and androstenedione in the follicular fluid from the Study and Control cycle did not vary but testosterone was significantly lower in the Study cycle. A lower Inhibin B in the Study cycle corresponds with the antral follicles being significantly smaller after priming, and this probably led to a longer stimulation time in the Study cycle. This contradicts the theory that androgen priming causes more FSH receptors on developing (antral up to preovulatory) follicles. Instead, we hypothesize that androgen priming rescued some small antral follicles that would have otherwise undergone atresia by the end of the previous menstrual cycle. The mechanism of action was likely an increase in androgen levels and FSH receptor expression within these small follicles, however, not enough to elevate androgen levels in serum. We retrieved significantly more oocytes in the Study cycle and the production of estradiol per follicle ≥10 mm on trigger day was comparable in the Study and Control cycle, suggesting that the rescued follicles were competent in producing oocytes and steroid hormones. Limitations, reasons for caution The sample size was small, and androgen and Inhibin B levels were not the primary outcome. We have not demonstrated a higher androgen level or FSH receptor expression in small antral follicles following hCG-priming. Wider implications of the findings The results make us question the mechanism of action behind hCG-priming prior to IVF. It is important to design a study with retrieval of small antral follicles immediately after priming to investigate the proposed hypothesis and to confirm improved cycle outcomes i.e., more retrieved oocytes in a larger study population. Trial registration number NCT04643925

Evaluation of Some Serum Biochemical Indices in Patients with Gestational Diabetes

The aim of this study was to evaluate some serum biochemical indices in patients with gestational diabetes. Among the study's participants were 100 expectant mothers ranging in age from 24 to 35 who had been diagnosed with diabetes at a maternity hospital or pregnancy center in Baghdad city. According to their previous menstrual cycle or an ultrasound, these ladies were between 28 and 33 weeks pregnant. There were two categories of pregnant women: Twenty pregnant women in good health comprised (control group). Eighty GDM-pregnant women were enrolled. The current results showed a significant increase in levels of glucose, cholesterol, triglyceride, ALT, bilirubin, uric acid, and creatinine in the GDM group as compared with control patients, also a significant decrease in the levels of Albumin, HDL in GDM group as compared with control group. There were no significant differences in the levels of urea and AST in both GDM and control groups. In conclusion, there was a significant increase in levels of glucose, cholesterol, triglyceride, ALT, bilirubin, uric acid, and creatinine in the GDM group.

Perspectives on relative energy deficiency in sport (RED-S): A qualitative case study of athletes, coaches and medical professionals from a super league netball club.

Research into relative energy deficiency in sport (RED-S) has increased substantially over recent years given the impact on athletes' health and performance. Most studies have considered sports that place emphasis on the aesthetics, endurance, or weight-restriction. Fewer studies exist in team sports. Netball is a team sport yet to be explored despite players potentially being at risk of RED-S given the high training volumes, sporting culture, internal and external pressures, and small network of coaches and medical professionals. A qualitative case study was used to explore the perspective of athletes, coaches, and medical professionals on RED-S. Semi-structured interviews were conducted with 13 players, 4 coaches and 4 medical professionals affiliated to a Super League club. Interviews were recorded and transcribed verbatim. The data was analysed using thematic analysis. Five main themes were identified in this study. Awareness of RED-S amongst athletes and coaches was generally inadequate whereas medical professionals had some awareness of RED-S. Some athletes used contraception to reduce discomfort/pain during menstruation whilst others expressed concerns around long-term contraceptive use and previous menstrual cycle disturbance. Sporting demands, individual and contextual factors, and a preoccupation with body image were associated with nutritional restriction, whilst appearance was a source of internal and external pressure. External pressures also extended to coaches, assessments/feedback, social media, and commentary. Strategies suggested to reduce the risk of RED-S included "hard hitting cases", multidisciplinary team involvement, and support from the governing body. The findings of this study provide insight into factors potentially associated with the risk of RED-S from an athletes, coaches, and medical professional perspective. This insight can be used to increase overall awareness of RED-S in key stakeholders as well as improve the recognition for the pressures netball athletes face that might alter the level of risk.

The effect of growth hormone addition protocols to poor ovarian responders in in vitro fertilization cycles.

In vitro fertilization failure (IVF) is high in women with poor ovarian response or non-responder. For this reason, the addition of adjuvant treatments to IVF protocols has come to the fore. We assessed to investigate the effects of adjuvant GH therapy initiated in the mid-luteal phase on IVF success in poor ovarian response or non-responder women. A retrospective study was performed in 93 poor ovarian response or non-responder women from a single center. GH treatment was added (GH-plus group) in the mid-luteal phase of the previous menstrual cycle to 47 of the women who underwent controlled ovarian stimulation with the flexible antagonist protocol. 46 women, as another group, were applied to a flexible antagonist-only protocol (GH-free group). The IVF outcome results were evaluated and compared within the groups. The number of retrieved oocytes was statistically significantly higher in the GH-plus group (2.28±1.975) than in the GH-free group (1.24±1.728) (p=0.01). Although statistically insignificant (p=0.55), the clinical pregnancy rate was higher in the GH-plus group [(8/47), 17%] than in the GH-free group [(5/46, 11%]. The cancellation rate was statistically significantly higher in the GH-free group (65.2%) than in the GH-plus group (44.7%) (p=0.04). No oocyte retrieved cycle rate was higher in the GH-free group (56%) than in the GH-plus group (25%) (p=0.002). Adjuvant GH therapy administration to IVF protocol in the mid-luteal phase gives poor ovarian response or non-responder women a chance to have a baby.

Ichthyosis Uterus – A Rare Premalignant Lesion of Endometrium

Ichthyosis (ikTHeosis) uterus is a rare benign metaplastic transformation of uterine endometrium into stratified squamous epithelium. The word ichthyosis (plural ichthyoses) comes from two ancient Greek (ixtus), meaning fish and disease. The metaplastic epithelium is parakeratotic with absent granular layer. Premalignant potential of this benign transformation has not been established due to the rarity of occurrence. We report a case of 72 year old female, post menopausal with the complaints of painless lower abdominal distension for past six months. She had no history of menorrhagia or dysmenorrhea in her previous menstrual cycles. USG abdomen was done. She was taken up for elective hysterectomy with a diagnosis of hydrometra. Total abdominal hysterectomy with bilateral salpingo-oophorectomy with pelvic lymph node sampling done. Peritoneal fluid cytology, peritoneal biopsy was done. Gross section of specimen was seen and the same sent for histopathological examination. Based on these histological findings a diagnosis of Ichthyosis uteri with focal High grade Squamous intraepithelial lesion of endometrium was made. In our case, there is a direct continuity of the squamous metaplasia of the endocervix and the endometrial lining. This supports the benign metaplastic spread of squamous epithelium from the transformation zone of the cervix into the uterine cavity. However, the stimulation of squamous metaplasia in uterine endometrium as a result of long term hydrometra is being hypothesised in our patient. The association of hydrometra, squamous metaplasia and dysplastic changes in endometrium are speculated.

Intact luteinizing hormone (LH), LHβ, and LHβ core fragment in urine of menstruating women.

We examined different molecular forms of luteinizing hormone (LH) in urine samples taken during periovulatory days with the aim of revealing different forms of LH immunoreactivity (LH-ir) in normally menstruating women. Serum and first-morning-voided urine serum samples were obtained from six healthy, 22 to 38 years old, regularly menstruating women during their periovulatory days based on their previous menstrual cycles. The day of the LH surge was determined on the basis of serum LH concentrations and confirmed by an at least two-fold increase in urinary concentrations of intact LH on consecutive days. Different molecular forms of LH-ir were identified by gel filtration of first-morning-voided urine samples obtained from regularly menstruating women on periovulatory days. Different forms of LH immunoreactivity (LH-ir) were distinguished as intact LH, its free beta-subunit (LHβ), and the core fragment of LHβ (LHβcf) according to their molecular sizes. The latter two are also called non-intact LH. Intact LH was the dominating form on the day before and on the day of LH surge while LHβcf was the major form of LH immunoreactivity after the LH surge for the following 5-7 days. LHβ was detected on the day of the LH surge as well as on the following day. These results indicate that LH is degraded in the kidneys and excreted as LHβ, and mainly as LHβcf for 7 days following the LH peak.

Case Report on Management of Abnormal Uterine Bleeding with Anemia

Introduction: The most prevalent condition seen in the gynecology outpatient department is abnormal uterine bleeding (AUB). AUB can be caused by a variety of conditions 1. A 42 year female who have chief complaints of abnormal uterine bleeding is bleeding from the uterus that is longer than usual or that occurs at an irregular time. several characteristics of underlying hereditary or acquired blood disorders increase the "anticipated" hormonal imbalance at this age, hence worsening the morbidity of the underlying condition axis .Despite the fact that blood problems can cause AUB, uterine structural and/or endocrine abnormalities are frequently missed when a blood illness is present [1]. Hematologists and gynecologists, as well as adolescent medicine experts, must work to get her to treat a complex etiology [2,3].&#x0D; Patient History: A 42 year old female was admitted in AVBRH in gynec ward sawangi meghe wardha with chief complaint of abnormal uterine bleeding since 2 month, abdominal pain since 1 week, weakness.&#x0D; Medical Management: Patient treated with anticoagulant, antibiotic, iron supplement.&#x0D; Nursing Management: Administrative IV fluid monitor vital sign, and medication given by doctor’s order.&#x0D; Conclusion: Women should be asked about their previous menstrual cycle, regularity, desire for reproduction, contraception, and sexual health by their primary care providers. If abnormal uterine bleeding is detected at the primary care level, additional history, examination, and testing can be undertaken, and appropriate consultations can be scheduled. Timely treatment and management of abnormal uterine bleeding with anemia.

P–312 Clinical applications of platelet-rich plasma in poor endometrium patients with adenomyosis

Abstract Study question Does the intrauterus application of platelet-rich plasma (PRP) allow improving the thickness of endometrium in patients with adenomyosis: comparative characteristics of the PRP-techniques? Summary answer The endometrial thickness in poor-endometrium-patients is increased after subendometrial PRP- injection comparing with the endometrium size after PRP- irrigation of the uterine cavity (P &amp;lt; 0.05). What is known already The endometrium plays an important role in achieving optimal outcomes of assisted reproductive technologies. PRP is a novel method that is used in reproductive medicine to improve the IVF outcome. The mechanisms of PRP have not been completely elucidated, but laboratory studies have shown that the high concentration of growth factors in PRP can potentially speed up the healing process. Recently, the intrauterine PRP-infusion and the subendometrial PRP-injection during the hysteroscopy have been described as a way to promote endometrial growth and receptivity. Study design, size, duration Totally 64 patients with adenomyosis and poor endometrium (≤ 6 mm) were divided into three experimental groups depending on PRP administration: intrauterine PRP-infusion, subendometrial PRP-injection and standard hormonal therapy of adenomyosis without PRP application. The period of study – December 2019 – November 2020. The study’s protocol was approved by the Center’s IRB. Participants/materials, setting, methods Intrauterine PRP-infusion was performed for 23 patients with age 34.2±3.6 y.o. (Group 1). Subendometrial PRP-injection was applied for 16 patients with the middle age 32,6±2,4 y.o. (Group 2). Additional hormonal therapy was carried out for patients from Groups 1, 2. The third control Group 3 consisted of 25 adenomyosis women with the middle age 35.7±4.1 y.o. Only the hormonal therapy was performed for patients of the control group. Main results and the role of chance The procedure of intrauterine PRP-infusion was done using the intrauterine catheter on the 8th and 12th days of the f hormone replacement therapy. Subendometrial PRP-injection was performed during the hysteroscopy on the 8th–10th day of the previous menstrual cycle. The control of the endometrium size was done by ultrasound examination. T-test was used for data analysis. P &amp;lt; 0.05 was considered statistically significant. After subendometrial PRP-injection, the average endometrium thickness was significantly higher comparing with the control (8.7±1.1mm vs. 5.8±0.8mm) (Student t-test t = 2.13, P = 0.04). PRP-infusion also showed significantly strong positive result comparing with the control group (8.3±0.9mm vs. 5.8±0.8mm) (Student t-test t = 2.08, P = 0.043). There is the tendency that subendometrial PRP-has a greater impact on endometrium size comparing with the PRP-infusion. Further investigations should be done. Limitations, reasons for caution Patients with Asherman’s syndrome were excluded from experiment. Wider implications of the findings: It is not clear how the intrauterine administration of PRP may act to affect endometrial thickness. Results from studies on the role of endometrial thickness on implantation and live births are contradictory. There is the urge for well-designed randomized studies to improve our knowledge on PRP in reproductive medicine. Trial registration number -

The Role of Traditional Chinese Formula Ding-Kun Pill (DKP) in Expected Poor Ovarian Response Women (POSEIDON Group 4) Undergoing In Vitro Fertilization-Embryo Transfer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

ObjectiveThe primary objective of the study was to assess traditional Chinese formula DKP supplementation in terms of efficacy and safety on reproductive outcomes of expected poor ovarian responder (POR, POSEIDON Group 4) undergoing in vitro fertilization-embryo transfer (IVF-ET).Design, Setting, and ParticipantsWomen eligible for IVF-ET were invited to participate in this randomized, double-blind, placebo-controlled, superiority trial at academic fertility centers of ten public hospitals in Chinese Mainland. A total of 462 patients (35–44 years) equally divided between DKP and placebo groups with antral follicle count (AFC) <5 or anti-müllerian hormone (AMH) <1.2 ng/ml were randomized.InterventionsAll participants were given DKP or 7 g placebo twice daily on the previous menstrual cycle day 5 until oocyte retrieval, which took approximately 5 to 6 weeks.Main Outcome MeasureThe primary outcome was the ongoing pregnancy defined as more than 20 gestational weeks of an intrauterine living fetus confirmed by pelvic ultrasonography.ResultsDemographic characteristics were equally distributed between the study populations. Intention-to-treat (ITT) analysis revealed that ongoing pregnancy rate (OPR) was not significantly different between DKP and placebo groups [26.4% (61/231) versus 24.2% (56/231); relative risk (RR) 1.09, 95% confidence interval (CI) 0.80 to 1.49, P = 0.593]. No significant differences between groups were observed for the secondary outcomes. The additional per protocol (PP) analysis was in line with ITT results: OPR in DKP group was 27.2% (61/224) versus 24.1% (55/228) in placebo group [RR 1.13, 95%CI (0.82 to 1.55), P = 0.449]. After subgroup analysis the findings concluded that POR population of 35–37 years had a significantly higher OPR after 5–6 weeks of oral DKP (41.8%, 33/79) versus placebo (25.4%, 18/71) [RR 1.65, 95% CI (1.02 to 2.65), P = 0.034, P for interaction = 0.028].ConclusionThis well-designed randomized controlled trial (RCT) offers new high-quality evidence to supplement existing retrospective literature concerning DKP performance in expected PORs. DKP could be recommended as a safe and natural remedy for expected PORs (aged 35–37 years) who fulfill the POSEIDON group 4 criteria. However, additional interventional clinical studies are undoubtedly required to be conducted in the future to validate this hypothesis.Clinical Trial Registration www.chictr.org.cn, identifier ChiCTR1900026614.

Female Voice-Related Sexual Attractiveness to Males: Does it Vary With Different Degrees of Conception Likelihood?

Previous investigations have found that female voice-related attractiveness to males increases when both conception likelihood (CL) and voice fundamental frequency (fo) are elevated. To test this hypothesis, we conducted a perceptual experiment where 78 heterosexual males rated sexual attractiveness of 9 female voice samples, recorded at menstrual, follicular and luteal phases of the menstrual cycle under two double-blinded randomly allocated conditions: a natural menstrual cycle (placebo condition) and when using an oral contraceptive pill (OCP condition). The voice samples yielded a total of 54 stimuli that were visually sorted and rated using Visor software. Concentrations of estrogens, progesterone and testosterone were analyzed, and measurements of speaking fundamental frequency (sfo) and its standard deviation (sfoSD), fo derivative (dfo) and fo slope were made. A multilevel ordinal logistic regression model nested in listeners and in females, and adjusted by phase and condition, was carried out to assess the association between ratings and: (1) phases and conditions; (2) sex steroid hormonal concentrations; and (3) voice parameters. A high probability of obtaining high ratings of voice sexual attractiveness was found for: (1) menstrual phase of placebo use and follicular phase of OCP use; (2) for low estradiol to progesterone ratio and testosterone concentrations; and (3) for low dfo. The latter showed a moderate statistical association with ratings of high attractiveness, as compared with the small association found for the remaining variables. It seems that the voice is a weak cue for female CL. Female sexual attraction to males may be a consequence of what females do in order to regulate their extended sexuality across the menstrual cycle rather than of estrus cues, the use of paralinguistic speech patterns being an example.

Growth hormone alleviates oxidative stress and improves the IVF outcomes of poor ovarian responders: a randomized controlled trial

BackgroundOxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders.MethodsThis study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared.ResultsEndometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group (P < 0.05). Moreover, compared to those in the non-POR group, FF malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI) and ROS levels in GCs were significantly higher, whereas superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were significantly lower in the POR-C group (P < 0.05). Furthermore, compared with those in the POR-C group, the FF TAC was significantly increased in the POR-GH group, and TOS, OSI and intracellular ROS levels were significantly reduced (P < 0.05).ConclusionsPretreatment with GH alleviates OS and improves oocyte quality and IVF outcomes of poor ovarian responders.Trial registrationChinese Clinical Trial Registry. ChiCTR1900021269. Registered 8 February 2019, http://www.chictr.org.cn/edit.aspx?pid=35837&htm=4.

Follicular phase length has no influence on frozen-thawed embryo transfers in natural cycles

BackgroundWhether menstrual variability in women with regular and ovulatory cycle could affect embryo implantation remains controversial, with conflicting evidences presented in the literature. Thus, in this study, we evaluated the impact of prolonged follicular phase length (FPL) on the clinical pregnancy rate (CPR) after frozen–thawed embryo transfer (FET) in true natural cycles (NC).MethodsThis retrospective cohort study utilized data from a large university-affiliated reproductive medicine center. Women undergoing true NC-FET were grouped as per their FPL type: Prolonged FPL (n = 127) and Normal FPL (n = 737). The primary study outcome was CPR in these 2 groups.ResultsThe FPL in the current cycle was significantly longer in the Prolonged FPL group (23.0 ± 2.4) than in the Normal FPL group (16.0 ± 2.2; p < 0.001). The crude CPR was significantly higher in the Prolonged FPL group (61.4%) than in the Normal FPL group (51.7%; p = 0.043). After adjusting for the results of potential confounders including the age, BMI, percent of optimal embryos transferred, and endometrial thickness, the difference in the CRP between the 2 groups disappeared (OR 1.28, 95% CI: 0.86–1.91, p = 0.232). No statistically significant difference was noted in the rates of implantation and miscarriage.ConclusionsThe current FET should not be cancelled if the ovulation time exceeds the predicted period based on the length of the previous menstrual cycle in the light of no negative effect on the pregnancy outcome.

Mechanistic model of hormonal contraception.

Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.

Adenomyotic Cyst at Menopause Transition: A Combined Treatment

Cystic adenomyosis is a progressive, severe disease that causes medical resistant dysmenorrhea with a delay in diagnosis [1]. A 52-year-old woman presented to our clinic with a complaint of severe dysmenorrhea, an 8 on the visual analog score of pain, persisting for 1 year. Her previous menstrual cycles were regular and pain-free. There was no response to the oral progesterone therapy that she had for 6 months.

Efficacy and safety of Dingkun pill for female infertility patients with low prognosis undergoing in vitro fertilization-embryo transfer: study protocol for a multicenter, double-blind, randomized, placebo-controlled trial

BackgroundApproximately 15% of couples in the reproductive age are affected by infertility. Women with diminished ovarian reserves (DOR) or with a poor ovarian response (POR) are required to undergo in vitro fertilization and embryo transfer (IVF-ET) to achieve pregnancy. However, studies indicate that poor response to gonadotropin stimulation has been reported in women undergoing IVF-ET. Results from two recent clinical studies in China suggest that traditional Chinese medicine (TCM) formula Dingkun pill (DKP) showed a curative effect by improving the clinical pregnancy rate in women with DOR and POR. However, the heterogeneity of the studies does not allow one to draw a definitive conclusion on the therapeutic effect of DKP. Therefore, the purpose of this study was to investigate the effect of DKP on improving the clinical outcome of pregnancy of IVF-ET in women with low prognosis.MethodsA multicenter, double-blinded, randomized placebo-controlled trial was conducted. A total of 460 infertile patients undergoing IVF or intracytoplasmic sperm injection (ICSI) were recruited from 12 public hospitals in China. Participants were randomly divided into the experimental group (DKP formula) or the placebo group (control) at a ratio of 1:1. All patients were treated with GnRH antagonist protocol and ovarian stimulation performed for 5 weeks (from the 5th day of the previous menstrual cycle to the day of oocyte retrieval). The patients were followed up for 6 months to record their conception outcome. The primary outcome is to compare the pregnancy outcome to those under placebo treatment. Secondary outcomes included the total count of the retrieved oocyte, embryo quality, endometrial thickness on ET day, implantation rate, and early miscarriage rate.DiscussionCurrently, no multicenter, double-blind, randomized, placebo-controlled trials have been performed on the use of the DKP formula to improve on the clinical outcome of the conception of IVF-ET in women with low prognosis. DKP might provide a good clinical solution for females with low prognosis and undergoing IVF. There is no contemporary Western medicine to improve on the clinical outcome of conception in IVF-ET in women with low prognosis. Therefore, it is important to undertake a well-designed randomized trial to determine the effect of DKP in improving the clinical outcome of the conception of IVF-ET in women with low prognosis.Trial registrationChinese Clinical Trial Registry (ChiCTR). Trial registration number: ChiCTR1900026614. Registered on 16 October 2019.