Midfollicular Phase Research Articles

Aberrant Intrinsic Brain Network Functional Connectivity During a Face-Matching Task in Women Diagnosed With Premenstrual Dysphoric Disorder

BackgroundPremenstrual dysphoric disorder (PMDD) is characterized by affective, cognitive, and physical symptoms, suggesting alterations at the brain network level. Women with PMDD demonstrate aberrant discrimination of facial emotions during the luteal phase of the menstrual cycle and altered reactivity to emotional stimuli. However, previous studies assessing emotional task-related brain reactivity using region-of-interest or whole-brain analysis have reported conflicting findings. Therefore, we utilized both region-of-interest task-reactivity and seed-voxel functional connectivity (FC) approaches to test for differences in the default mode network, salience network, and central executive network between women with PMDD and control participants during an emotional-processing task that yields an optimal setup for investigating brain network changes in PMDD. MethodsTwenty-four women with PMDD and 27 control participants were classified according to the Daily Record of Severity of Problems. Participants underwent functional magnetic resonance imaging scans while completing the emotional face-matching task during the midfollicular and late-luteal phases of their menstrual cycle. ResultsNo significant between-group differences in brain reactivity were found using region-of-interest analysis. In the FC analysis, a main effect of diagnosis was found showing decreased default mode network connectivity, increased salience network connectivity, and decreased central executive network connectivity in women with PMDD compared with control participants. A significant interaction between menstrual cycle phase and diagnosis was found in the central executive network for right posterior parietal cortex and left inferior lateral occipital cortex connectivity. A post hoc analysis revealed stronger FC during the midfollicular than the late-luteal phase of PMDD. ConclusionsAberrant FC in the 3 brain networks involved in PMDD may indicate vulnerability to experience affective and cognitive symptoms of the disorder.

Premature progesterone elevation during the early and mid-follicular phases in fresh in vitro fertilization (IVF) cycles is associated with lower live birth, clinical pregnancy, and implantation rates.

Evaluate follicular phase progesterone elevation (≥ 1.5ng/mL) prior to trigger during IVF stimulation and its effects on live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in fresh IVF cycles. This was a retrospective cohort study within an academic clinic. A total of 6961 fresh IVF and IVF/ICSI cycles from October 1, 2015 to June 30, 2021 were included and grouped by progesterone (PR) prior to trigger: PR < 1.5ng/mL (low PR group) and PR ≥ 1.5ng/mL (high PR group). Main outcome measures included LBR, CPR, and IR. Among all cycle starts, 1568 (22.5%) were in the high PR group and 5393 (77.5%) were in the low PR group. Of the cycles which proceeded to an embryo transfer, 416 (11.1%) were in the high PR group and 3341 (88.9%) were in the low PR group. The high PR group had significantly lower IR (RR 0.75; 95% CI 0.64-0.88), CPR (aRR 0.74; 95% CI 0.64-0.87), and LBR (aRR 0.71; 95% CI 0.59-0.85) compared to the low PR group. When stratified by progesterone on the day of trigger (TPR), there was a clinically notable decrease in IR (16.8% vs 23.3%), CPR (28.1% vs 36.0%), and LBR (22.8% vs 28.9%) in the high PR group compared to the low PR group even when TPR < 1.5ng/mL. In fresh IVF cycles in which TPR < 1.5ng/mL, progesterone elevation ≥ 1.5ng/mL at any point in time prior to trigger negatively impacts IR, CPR, and LBR. This data supports testing of serum progesterone in the follicular phase prior to trigger, as these patients may benefit from a freeze-all approach.

Coordinating smoking cessation treatment with menstrual cycle phase to improve quit outcomes (MC-NRT): study protocol for a randomized controlled trial

BackgroundWomen experience greater difficulty achieving smoking abstinence compared to men. Recent evidence suggests that hormonal fluctuations during different phases of the menstrual cycle can contribute to lower smoking abstinence rates following a quit attempt among women. However, these findings are limited by small sample sizes and variability among targeted smoking quit dates. This clinical trial aims to clarify whether targeting the quit date to the follicular or luteal phase of the menstrual cycle can improve smoking abstinence.MethodsParticipants will enroll in an online smoking cessation program providing nicotine replacement therapy (NRT) and behavioral support. We will randomize 1200 eligible individuals to set a target quit date: (1) during the mid-luteal phase, (2) during the mid-follicular phase, or (3) 15–30 days after enrollment with no regard to the menstrual cycle phase (usual practice). Participants will receive a 6-week supply of combination NRT consisting of a nicotine patch plus their choice of nicotine gum or lozenge. Participants will be instructed to start using NRT on their target quit date. Optional behavioral support will consist of a free downloadable app and brief videos focusing on building a quit plan, coping with cravings, and relapse prevention, delivered via e-mail. Smoking status will be assessed via dried blood spot analysis of cotinine concentration at 7 days, 6 weeks, and 6 months post-target quit date.DiscussionWe aim to overcome the limitations of previous studies by recruiting a large sample of participants and assigning target quit dates to the middle of both the follicular and luteal phases. The results of the trial can further elucidate the effects of the menstrual cycle on smoking cessation outcomes and whether it is beneficial to combine menstrual cycle phase timing strategies with accessible and low-cost NRT.Trial registrationClinicalTrials.gov NCT05515354. Registered on August 23, 2022.

Alcohol use and motives for drinking across the menstrual cycle in a psychiatric outpatient sample.

Females who misuse alcohol experience high rates of negative physical and mental health consequences. Existing findings are inconsistent but suggest a relationship between ovarian hormones and alcohol use. We aim to clarify how alcohol use and drinking motives vary across the menstrual cycle in female psychiatric outpatients using the luteinizing hormone (LH)-confirmed cycle phase. Daily self-reports (n= 3721) were collected from 94 naturally cycling females, recruited for past-month suicidal ideation, during the baseline phase of three parent clinical trials between February 2017 and May 2022. Multilevel logistic and linear models estimated the relationship between the cycle phase (with LH-surge confirmed ovulation) and daily alcohol use or drinking motives, moderated by the weekend. Models were adjusted for age, legal drinking status, substance use disorder, and the COVID-19 pandemic, and included random effects. Participants were generally more likely to drink in the midluteal (vs. perimenstrual) phase, but more likely to drink heavily on weekends in periovulatory and perimenstrual (vs. midluteal) phases. Social motives for drinking were significantly higher on weekends in the periovulatory, mid-follicular, and midluteal phases (vs. weekdays), but this finding was non-significant in the perimenstrual phase. Participants rated drinking to cope higher in the perimenstrual phase (vs. midluteal phase), regardless of the weekend. In a psychiatric sample with LH-surge-confirmed ovulation, we find an increased likelihood to drink heavily in periovulatory and perimenstrual phases on weekends. We also find that the perimenstrual phase is associated with increased drinking to cope, and relatively lower weekend social drinking. Finally, random effects across models suggest individual differences in the extent to which the cycle influences drinking. Our findings stress (1) predictable phases of increased high-risk alcohol use across the menstrual cycle, and (2) the importance of individual assessment of cyclical changes in alcohol use to predict and prevent ovulation- and menses-related surges in heavy drinking.

The circadian variation of sleep and alertness of postmenopausal women.

Several factors may contribute to the high prevalence of sleep disturbances occurring in postmenopausal women. However, the contribution of the circadian timing system to their sleep disturbances remains unclear. In the present study, we aim to understand the impact of circadian factors on changes of sleep and alertness occurring after menopause. Eight healthy postmenopausal women and 12 healthy young women in their mid-follicular phase participated in an ultradian sleep-wake cycle procedure (USW). This protocol consisted of alternating 60-min wake periods and nap opportunities for ≥ 48 h in controlled laboratory conditions. Core body temperature (CBT), salivary melatonin, self-reported alertness, and polysomnographically recorded sleep were measured across this procedure. In both groups, all measures displayed a circadian variation throughout the USW procedure. Compared to young women, postmenopausal women presented lower CBT values, more stage N1 and N2 sleep, and number of arousals. They also showed a reduced amplitude of the circadian variation of melatonin, total sleep time (TST), sleep onset latency (SOL), stage N3 sleep, and alertness levels. Postmenopausal women fell asleep faster and slept more during the biological day and presented higher alertness levels during the biological night than young women. These results support the hypothesis of a weakened circadian signal promoting sleep and wakefulness in older women. Aging processes including hormonal changes may be main contributors to the increased sleep-wake disturbances after menopause.

Effects of time of recombinant luteinized hormone supplementation on pregnancy outcomes of women with advanced reproductive age during follicular-phase long protocol

Objective: To investigate the effects of supplementation of recombinant luteinized hormone (rLH) and its timing on pregnancy outcomes of patients at 35 years or older with follicular-phase long protocol. Methods: Clinical data of women undergoing in vitro fertilization or intracytoplasmic sperm injection with follicular-phase long protocol was collected and retrospectively analyzed in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2019. There were 558 patients at 35 years or older included in this study, and they were divided into three groups: group A was patients with only recombinant follicle stimulating hormone (rFSH) stimulation (127 cycles), group B was patients with rFSH plus rLH supplementation in the mid-follicular phase (141 cycles), and patients in group C received combined rFSH and rLH from the first day of ovarian stimulation (290 cycles). The basic characteristics of patients of each group were observed and the effects of ovarian simulation and pregnancy outcomes were compared among the three groups. Logistic regression model was performed to explore the association between different groups and pregnancy outcomes. Results: The basic characteristics such as age, duration of infertility, body mass index (BMI) and serum basic follicle stimulating hormone (FSH) were comparable among the three groups (all P>0.05). Anti-Müllerian hormone (AMH), antral follicles count (AFC) and basic luteinized hormone (LH) were significantly lower in group C compared to group A and group B (all P<0.05). There were statistically significant differences in initiation dosage, total dosage and duration of gonadotropin (Gn) among the three groups (all P<0.01), the initiation dosage, total dosage and duration of Gn were higher in group C than the other two groups. The number of oocytes retrieved and available embryos were significantly lower in group B and group C than group A (all P<0.001). In fresh embryo transfer cycles, significantly higher implantation rate (45.3%, 117/258) and clinical pregnancy rate (52.6%, 111/211) were found for group C when compared with group A and group B (P=0.036, P=0.006). The live birth rate in fresh embryo transfer cycles was comparable among the three groups (P=0.098). The implantation rate, clinical pregnancy rate and live birth rate in the subsequent frozen-thawed embryo transfer cycles did not differ significantly among the three groups (all P>0.05). There were no significantly differences in the cumulative pregnancy rate and the cumulative live birth rate among the three groups (all P>0.05). After adjusted for age, BMI, AMH, AFC, basic FSH and LH, total Gn dosage, endometrial thickness at transfer, number of oocytes retrieved, number of embryos transferred and stage of embryo transferred, in fresh embryo transfer cycles, the clinical pregnancy rate (adjusted OR=2.793, 95%CI: 1.512-5.162, P<0.001) and live birth rate (adjusted OR=2.324, 95%CI: 1.241-4.351, P=0.008) were higher in group C, while clinical pregnancy rate and live birth rate were similar between group B and group A in fresh embryo transfer cycles (all P>0.05); there was no significant difference in cumulative live birth rate among the three groups (P>0.05). Conclusions: The supplementation of rLH from the first day of ovarian stimulation improves the pregnancy outcomes of patients at 35 years or older in fresh embryo transfer cycles during follicular-phase long protocol. However, the supplementation of rLH has no benefit on cumulative live birth rate.

Uterine contractile activity in healthy women throughout the menstrual cycle measured using a novel quantitative two-dimensional transvaginal ultrasound speckle tracking method

Research questionTo explore normal uterine contractile function across the menstrual cycle using a novel quantitative ultrasound method. DesignThis multicentre prospective observational study took place in three European centres from 2014 to 2022. Uterine contraction frequency (contractions/minute), amplitude, direction (cervix-to-fundus, C2F; fundus-to-cervix; F2C), velocity and coordination were investigated. Features were extracted from transvaginal ultrasound recordings (TVUS) using speckle tracking. Premenopausal women ≥18 years of age, with normal, natural menstrual cycles were included. A normal cycle was defined as: regular (duration 28 ± 2 days), no dysmenorrhoea, no menometrorrhagia. Four-minute TVUS were performed during the menstrual phase, mid-follicular, late follicular phase, early luteal phase and/or late luteal phase. Of the 96 recordings available from 64 women, 70 were suitable for inclusion in the analysis. ResultsContraction frequency (for the posterior wall) and velocity (for the anterior uterine wall in the F2C direction) were highest in the late follicular phase and lowest in the menstrual and late luteal phases (1.61 versus 1.31 and 1.35 contractions/min, P < 0.001 and 0.81 versus 0.67 and 0.62 mm/s, P < 0.001, respectively). No significant difference was found for contraction amplitude. Contraction coordination (simultaneous contraction of the anterior and posterior walls in the same direction) was least coordinated in the mid-follicular phase (P = 0.002). ConclusionsThis is the first study to objectively measure uterine contraction features in healthy women during the natural menstrual cycle on TVUS. Likewise, it introduces contraction coordination as a specific feature of uterine peristalsis. Differences in uterine contractility across the menstrual cycle are confirmed, with highest activity seen in the late follicular phase, and lowest in the late luteal phase.

Ambulatory Glucose Profile According to Different Phases of the Menstrual Cycle in Women Living With Type 1 Diabetes.

Some women living with type 1 diabetes complain of changes in glucose values according to the different phases of menstruation. To evaluate this variability through continuous glucose monitoring (CGM) data in type 1 diabetes patients. Observational study. Ambulatory data, recruitment in 2 centers in the Paris region. Twenty-four women with type 1 diabetes having spontaneous menstrual cycles. Collection of CGM data for 62 spontaneous menstrual cycles, with evaluation of five 3-day phases during each cycle: (1) early follicular (menstruations), (2) mid-follicular, (3) peri-ovulatory, (4) mid-luteal, and (5) late luteal. Time in range (TIR, prespecified). TIR decreased for each consecutive phase (61 ± 18%; 59 ± 18%; 59 ± 20%; 57 ± 18%; and 55 ± 20%, P = 0.02). The linear mixed model highlighted a decrease in TIR in the mid-luteal (P = 0.03) and late luteal (P < 0.001) phases compared with the early follicular phase. Time above range was significantly higher during the late luteal phase than the early follicular phase (P = 0.003). Time below range was significantly higher during the mid-follicular phase than in the early follicular phase. In most of the study population, glucose levels rose linearly throughout the menstrual cycle, reaching a maximum in the late luteal phase. A sharp decrease was seen for most participants at the beginning of menstrual bleeding. This should be taken into consideration in daily care of type 1 diabetes patients to avoid hypoglycemia.

Obesity-induced follicular phase endometrial proteome dysregulation in a well-phenotyped population

Despite obesity's significant impact on reproduction, its influence on the physiology of the human endometrium is largely understudied. We hypothesized that endometrial proteomic differences exist between obese (OW; body mass index [BMI] ≥30 kg/m2) and normal-weight women (NWW; BMI, 18.5-24.9 kg/m2). Clinical cross-sectional study. Academic Medical Center. Healthy, normally-cycling, 18 to 40-year-old women (n = 6 OW and n = 6 NWW). Participants underwent screening and midfollicular phase visits. Demographic and anthropometric characteristics, blood samples, ultrasounds, and follicular phase endometrial biopsies were collected. Proteomic analyses of endometrial samples (liquid chromatography-mass spectrometry) were performed. Proteins with ≥2-fold difference and a false discovery rate of <0.1 were considered statistically significant (Benjamini-Hochberg adjustment). Reproductive hormone levels did not differ between the two groups. Mean BMI, serum leptin concentration, and bioelectrical impedance analysis indices of adiposity were higher in OW than in NWW. Histological examination of the endometrial samples confirmed normal-appearing endometrium in both OW and NWW. A total of 2,930 proteins were detected across all samples, with an average number of proteins per sample of 2,059 ± 482 in NWW and 2,437 ± 187 in OW. A total of 17 proteins were differentially expressed in OW vs. NWW; 2 were more abundant, whereas 15 were underexpressed in OW, including the progesterone receptor. In this well-phenotyped population of healthy women, obesity was associated with significant endometrial proliferative phase proteomic differences affecting the hormonal and immunologic pathways. These could contribute to an increased risk of menstrual bleeding abnormalities and create an altered environment for future luteinization.

Psychophysiological Responses to Self-Selected Exercise Intensity Over the Menstrual Cycle: A Randomized Crossover Phase Trial

ABSTRACT Purpose: This study investigated the psychophysiological responses during self-selected exercise intensity over the course of the menstrual cycle (MC). Methods: Seventeen healthy women with regular MCs completed three randomized treadmill bouts of 30 min of self-selected exercise intensity during menstruation, mid-follicular, and late luteal phases. Anxiety, menstrual distress (i.e., pain, behavior change, autonomic reaction, fluid retention, and negative affect) and profile of mood (i.e., tension, depression, and anger) were measured before exercise. Arousal, heart rate (HR), motivation, rating of perceived exertion and affective valence were measured before, during and after each exercise session. Results: Anger, anxiety, behavior change, pain, and negative affect were significantly greater (p < .05) during menstruation compared to the mid-follicular phase, whereas fluid retention, anger, behavior change, and autonomic reaction were greater (p < .05) during the late luteal phase compared with the mid-follicular phase. Participants felt more negative affective valence and less motivation to start exercise during menstruation compared with other MC phases. Average treadmill speed (5.8 ± 1.1 vs 6.0 ± 0.7 vs 5.9 ± 0.7 km/h–1, p = .36) and %HRmax (74.9 ± 3.2 vs 77.8 ± 5.4 vs 77.4 ± 7.1%, p = .40) did not differ between menstruation, mid-follicular, and late luteal phases. Also, noteworthy is that participants self-selected an intensity that exceeded the minimum levels recommended for health and cardiorespiratory fitness promotion (64–70% HRmax). Conclusions: Results of this study indicate that psychophysiological responses are negatively impacted mainly during menstruation and the late luteal phase of the MC. These findings may be helpful for professionals who work to promote the initiation and maintenance of exercise in women.

Definition of large niche after Cesarean section based on prediction of postmenstrual spotting: Chinese cohort study in non-pregnant women.

A large niche after Cesarean section (CS) is associated with long-term complications, of which postmenstrual spotting is associated positively with the size of the niche. However, the diagnosis of a large niche in the literature is inconsistent and the definition is largely subjective. The aim of this study was to generate a definition for a large niche in non-pregnant women based on the presence of postmenstrual spotting. Women who had undergone CS in our hospital between January 2012 and June 2017 were selected randomly from our database, contacted by telephone and subsequently examined between January 2016 and June 2020. Eligible for inclusion were non-pregnant women who had their last CS more than 1 year earlier and agreed to undergo transvaginal sonography(TVS). All participants underwent examination of their CS scar by TVS (two-dimensional color Doppler) during the midfollicular phase. Niche depth, length, width, residual myometrial thickness (RMT), adjacent myometrial thickness (AMT) and ratio of niche depth/AMT were recorded. Women diagnosed with a niche, defined as an indentation at the site of the CS with a depth of at least 2 mm, were classified into two groups (symptomatic or asymptomatic) according to whether they experienced postmenstrual spotting. Logistic regression analysis was used to establish the best cut-off values for the niche parameters to predict postmenstrual spotting. A new definition was generated based on the niche parameters with the highest area under the receiver-operating-characteristics (ROC) curve (AUC) for the prediction of postmenstrual spotting. A total of 727 women who had a CS > 1 year earlier underwent TVS examination, of whom 263 were diagnosed with a niche (prevalence of 36.2%). Of these, 160 women experienced postmenstrual spotting and 103 were asymptomatic. The three variables with the highest AUC for prediction of postmenstrual spotting were niche depth/AMT ratio (AUC, 0.798; 95% CI, 0.745-0.852), niche depth (AUC, 0.731; 95% CI, 0.668-0.795) and RMT (AUC, 0.683; 95% CI, 0.618-0.748). Based on the best cut-offs according to ROC-curve analysis, a large niche was defined as: niche depth ≥ 0.50 cm, RMT ≤ 0.21 cm or niche depth/AMT ratio ≥ 0.56. The prevalence of a large niche according to this definition was 22.4% (163/727). The new definition had a specificity of 61.17% (95% CI, 52.34-70.41%) and sensitivity of 76.87% (95% CI, 70.28-84.16%) for a large niche. This study has provided a new definition for a large niche after CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Carbohydrate-Energy Replacement Following High-Intensity Interval Exercise Blunts Next-Day Glycemic Control in Untrained Women.

BackgroundImproved glycemic control has been reported for ∼24 h following low-volume high-intensity interval exercise (HIIE), but it is unclear if this is a direct effect of exercise or an indirect effect of the exercise-induced energy deficit. The purpose of this study was to investigate the effect of carbohydrate-energy replacement after low-volume HIIE on 24 h glycemic control in women.MethodsSeven untrained women (age: 22 ± 2 yr; BMI: 22 ± 3 kg/m2; VO2peak: 33 ± 7 ml/kg/min) completed three 2-day trials in the mid-follicular phase of the menstrual cycle. Continuous glucose monitoring was used to measure blood glucose concentrations during, and for 24 h following three conditions: (1) HIIE followed by a high-carbohydrate energy replacement drink (EX-HC); (2) HIIE followed by a non-caloric taste-matched placebo drink (EX-NC); and (3) seated control with no drink (CTL). HIIE involved an evening session (1,700 h) of 10 × 1-min cycling efforts at ∼90% maximal heart rate with 1 min recovery. Diet was standardized and identical across all three 2-day trials, apart from the post-exercise carbohydrate drink in EX-HC, which was designed to replenish the exercise-induced energy expenditure. Postprandial glycemic responses to the following days breakfast, snack, lunch, and dinner, as well as 24 h indices of glycemic control, were analyzed.ResultsThe day after HIIE, postprandial glycemia following breakfast and snack were reduced in EX-NC compared to EX-HC, as reflected by lower 3 h glucose mean (breakfast: 5.5 ± 0.5 vs. 6.7 ± 1, p = 0.01, Cohen’s d = 1.4; snack: 4.9 ± 0.3 vs. 5.7 ± 0.8 mmol/L, p = 0.02, d = 1.4) and/or area under the curve (AUC) (breakfast: 994 ± 86 vs. 1,208 ± 190 mmol/L x 3 h, p = 0.01, d = 1.5). Postprandial glycemic responses following lunch and dinner were not different across conditions (p > 0.05). The 24 h glucose mean (EX-NC: 5.2 ± 0.3 vs. EX-HC: 5.7 ± 0.7 mmol/L; p = 0.02, d = 1.1) and AUC (EX-NC: 7,448 ± 425 vs. EX-HC: 8,246 ± 957 mmol/L × 24 h; p = 0.02, d = 1.1) were reduced in EX-NC compared to EX-HC.ConclusionPost-exercise carbohydrate-energy replacement attenuates glycemic control the day following a single session of low-volume HIIE in women.

Dynamics of vaginal microbiota in women of reproductive age during the menstrual cycle

Objective: To investigate the dynamic changes of vaginal microbiota in different phases of menstrual cycle in healthy Chinese women of childbearing age. Methods: A total of 11 healthy women of childbearing age with regular menstruation, who had physical examination in the Gynecology Clinic of Beijing Obstetrics and Gynecology Hospital from September to December 2020 were randomly selected as research subjects. Vaginal secretions were collected during menstrual phase (2nd-3rd day), mid-follicular phase (7th-8th day), and mid-luteal phase (21st-22nd day) for microbiota analysis through metagenomic sequencing. Results: (1) Vaginal microbiota species were the most diverse in menstrual phase and the least in follicular phase, observing dominant vaginal bacteria gradually changing to Lactobacillus from menstrual phase to follicular phase and then to luteal phase. (2) The dynamic evolution of vaginal microbiota from menstrual phase to follicular phase and then to luteal phase was divided into: no change in dominant bacteria, replacement of dominant bacteria, changes in the proportion of dominant bacteria, and recurrence of dominant bacteria (non-Lactobacillus-dominance appeared again in luteal phase after returning to normal Lactobacillus-dominance in follicular phase). (3) Prevotella, especially Prevotella_bivia, was significantly higher during menstrual phase. Conclusions: Healthy vaginal microbiota should be relatively stable, but also have the ability of dynamic change and self-recovery. Prevotella plays a central role among opportunistic pathogens in the vagina, whose function remains to be investigated.

Whole and segmental body composition changes during mid-follicular and mid-luteal phases of the menstrual cycle in recreationally active young women

Background Changes in oestradiol and progesterone hormones and associated fluid retention during the menstrual cycle phases might affect body composition (BC) in women. Aim The main objectives of this study were to determine the changes in whole and segmental BC by dual-energy x-ray absorptiometry (DXA) and bioelectrical impedance (BIA) during the mid-follicular (MFP) and mid-luteal (MLP) phases. Subjects and methods Thirty recreationally active young women participated in this study. BC was measured by DXA and BIA during MFP and MLP. A mixed linear model for repeated measures analysis was used to determine the differences between the two phases. Results Body mass was higher during MLP than MFP, while total body water, total and segmental fat mass and fat percentages measured by both BIA and DXA were similar during the two phases. DXA-derived fat-free mass and soft lean mass in the android region were higher during MLP than MFP. Large variability in individual responses was evident. Conclusion On average, whole and segmental BC variables do not change significantly between MFP and MLP. However, given the large variability among the individual responses, it is suggested to perform repeated BC measurements during the same phase of the menstrual cycle.

Uterine Cavity Irrigation With Office Hysteroscopy During Ovarian Stimulation for IVF: A Randomized Controlled Trial.

ObjectiveThis was a non-blinded randomized controlled study to evaluate whether endometrial irrigation via office hysteroscopy during the early follicular phase would lead to a higher level of live birth rates compared to no irrigation in the fresh embryo transfer cycle.MethodThe study was conducted in Tehran university of medical sciences from June 2015 to June 2016. women under the age of 40 with primary infertility without history of previous IVF/ICSI or hysteroscopic examination, were included. Controlled ovarian hyperstimulation was done. Hysteroscopy was performed in the early mid-follicular phase of a stimulation cycle (day 5-7) with a vaginoscopy approach and saline irrigation in hysteroscopy group. Embryo-transfer was done in the same cycle.Results228 patients completed their participation in the study. In the fresh cycle, clinical pregnancy rate was 46% in the hysteroscopy group and 40.43% in the control group. (p-value= 0.326, RR= 1.16 [95%CI: 0.862 to 1.56]). Live birth rate was 41.28% in the hysteroscopic group and 31.93% in the control group (p-value=0.143, RR= 1.293 [95%CI: 0.916 to 1.825]). For those patients having surplus cryopreserved embryos, after 2 months, a second embryo transfer was performed. The cumulative LBR was 44.05% in the hysteroscopic group and 32.25% in the control group (p-value=0.029, RR= 1.368 [95%CI: 1.031 to 1.815], RD= 11.9% [95%CI: 1.2% to 22.3%] and NNT= 8 [95%CI: 4 to 85]).ConclusionThe current study clearly demonstrated a significantly higher cumulative live birth rate in the intervention group.Clinical Trial Registration[https://www.irct.ir/trial/19586], identifier IRCT2016011022795N2.

Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes.

To investigate whether the timing of rLH addition to rFSH during controlled ovarian stimulation (COS) impacts ovarian response and the outcomes of intracytoplasmic sperm injection (ICSI) cycles. Data of 1278 patients undergoing ICSI between 2015 and 2018, in a private university-affiliated IVF center were analyzed. Patients were divided into groups according to the timing of LH addition to the COS protocol: Group LH-start (n=323), in which LH was administered since day 1 of ovarian stimulation; and Group LH-mid (n=955), in which LH was administered concomitantly with gonadotropin releasing hormone (GnRH) antagonist. Data were also stratified according to female age and response to COS. The outcomes of COS and ICSI were compared between the groups. For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were in Group LH-mid compared to Group LH-start. In patients with poor response to COS (POR), higher fertilization rate, blastocyst development rate and implantation rate were observed in Group LH-mid. rLH supplementation in POR patients may improve laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles.

Random antral follicle count performed on any day of the menstrual cycle has the same predictive value as AMH for good ovarian response in IVF cycles

ObjectiveTo determine whether the predictive value of AFC for ovarian response to stimulation for IVF depends on the day of the menstrual cycle when ultrasound is performed. Methods410 women undergoing their first IVF cycle were included. All the women had AFC performed twice. The first measurement, random AFC (r-AFC), was performed during the fertility workup whatever the day of their menstrual cycle. Three groups were constituted according to the period of ultrasound performance: at early follicular phase i.e., day 1 to day 6 (eFP-AFC); at mid follicular phase i.e., day 7 to 12 (mFP-AFC) and at luteal phase i.e., day 13 or after (LP-AFC). A second AFC measurement was performed before the start of the ovarian stimulation (SD1-AFC). AMH dosing was done in the early follicular phase. ResultsRandom AFC (r-AFC) was correlated to AMH (r = 0.69; p<0.001), SD1-AFC (r = 0.75; p<0.001) and number of oocytes retrieved (r = 0.49; p<0.001). When regarding AFC depending on the cycle day group, the correlation with AMH was 0.65, 0.66 and 0.85 for the eFP-AFC, the mFP-AFC and the LP-AFC respectively (all p were <0.001). The ROC analysis showed the same predictive value for good ovarian response (more than 6 oocytes retrieved) for the eFP-AFC, mFP-AFC and LP-AFC (AUC 0.73, 0.75 and 0.84 respectively; p = 0.28). The AUC of r-AFC (0.76) were similar to those of AMH (0.74) and SD1-AFC (0.74) (p = 0.21 and 0.92 respectively). ConclusionAFC is strongly correlated with AMH and highly predictive of good ovarian response during the whole menstrual cycle.

PREMATURE PROGESTERONE ELEVATION DURING EARLY AND MID FOLLICULAR PHASES IN FRESH IN VITRO FERTILIZATION (IVF) CYCLES IS ASSOCIATED WITH LOWER IMPLANTATION AND CLINICAL PREGNANCY RATES

Despite routine suppression of endogenous gonadotropins by gonadotropin-releasing hormone (GnRH) agonists and antagonists, progesterone elevation (PE) at the time of trigger is common during controlled ovarian stimulation. Prior studies have found PE on the day of trigger to adversely affect implantation in fresh IVF cycles; however, these studies failed to capture the impact of PE in the early and mid-follicular phases. The objective of this study was to evaluate and characterize early and mid-follicular phase PE (>1.5 ng/mL) during IVF stimulation and its effects on implantation and clinical pregnancy rates in fresh IVF cycles, irrespective of the serum progesterone level on the day of trigger (TPR).

P–599 random antral follicle count, performed at any day of the menstrual cycle, demonstrates the same predictive value for ovarian response in in vitro fertilization cycles

Abstract Study question Does antral follicle count (AFC) retains its predictive value for ovarian response to stimulation for in vitro fertilization (IVF) throughout the whole menstrual cycle? Summary answer AFC is strongly correlated to anti-mullerian hormone (AMH) and highly predictive of good ovarian response whatever the day of cycle the ultrasound is performed. What is known already Usually performed in the early follicular phase (at day 2–3 of the menstrual cycle), AFC and AMH are the most accurate markers of ovarian reserve. They are routinely used to predict ovarian response to ovarian stimulation for IVF and eventually to individualize the gonadotropin starting dose. Study design, size, duration Retrospective cohort study performed between January, 2017 and December, 2019. Participants/materials, setting, methods 410 consecutive women aged 20 to 42 years were included. Random AFC (r-AFC) was performed during the fertility workup whatever the day of their menstrual cycle was: early follicular phase i.e. day 1 to day 6 (eFP-AFC), mid follicular phase i.e. day 7 to 12 (mFP-AFC) and luteal phase i.e. day 13 or after (LP-AFC). A second AFC was performed before the start of the stimulation (SD1-AFC). AMH was measured in the early follicular phase. Main results and the role of chance Random AFC (r-AFC) was correlated to AMH (r = 0.692; p &amp;lt; 0.001), SD1-AFC (r = 0.756; p &amp;lt; 0.001) and number of oocytes retrieved (r = 0.491; p &amp;lt; 0.001). When regarding AFC depending on the cycle day group, the correlation with AMH was significantly higher for the LP-AFC, (LP-AFC) (r = 0.853) than for the eFP-AFC (r = 0.657; p &amp;lt; 0.001) and for the mFP-AFC (r = 0.668). The correlation with SD1-AFC was similar regardless of the time of performance of r-AFC (r = 0.739, 0.783, 0.733, respectively for eFP, mFP and LP-AFC). Moreover, the ROC analysis showed the same predictive value for good ovarian response (more than 6 oocytes retrieved) for the eFP-AFC, mFP-AFC and LP-AFC (AUC 0.73, 0.75 and 0.84 respectively) as well as for AMH and SD1-AFC (AUC 0.74 and 0.74, respectively). Limitations, reasons for caution This is a retrospective analysis, however data were prospectively collected and the method for ultrasound acquisition of AFC was standardized. Wider implications of the findings: The absence of significant variation of AFC across the menstrual cycle allows to its random performance. Ultrasound performed besides early follicular phase discloses informations on ovaries, the uterus and the endometrium. It is more comfortable and convenient for women and physicians by limiting targeted appointment during menstruation and reiterated examination. Trial registration number Not applicable

P–594 Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes

Abstract Study question Is there an impact of recombinant luteinizing-hormone (rLH) administration timing during controlled ovarian stimulation (COS) on ovarian response and intracytoplasmic sperm injection (ICSI) cycles outcomes? Summary answer rLH supplementation in patients with poor ovarian response (POR) improves laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles. What is known already Meta-analyses demonstrated that the use of rLH combined with rFSH for COS may lead to more ongoing pregnancies than rFSH alone. However, there is limited evidence that the timing of rLH addition to rFSH may impact the ovarian response or the outcomes of ICSI, based on a limited casuistic, which demonstrated improved ovarian response, embryo quality and pregnancy rate with LH supplementation from GnRH antagonist administration day, in estimated POR patients. The objective of the present study was to further investigate this hypothesis in a larger population, and in subpopulations of patients stratified by age and response to COS. Study design, size, duration This historical cohort study included data obtained via chart review of 1278 ICSI cycles performed in 1278 patients between 2015 and 2018, in a private university-affiliated in vitro fertilization center. Post hoc power analysis was calculated, given α of 5%, sample size of 1278, and effect size for implantation rate. The achieved power was superior to 99%. Participants/materials, setting, methods Two groups were formed according to timing of LH administration: Group LH-start (n = 323), in which LH was started on day–1; and Group LH-mid (n = 955), in which LH was started with GnRH antagonist. Then, data were stratified according to female age (&amp;lt;35 years-old, n = 283, and ≥35 years-old, n = 995) and response to COS (poor response (POR): ≤4 retrieved oocytes, n = 423, and normal response: &amp;gt;5 retrieved oocytes, n = 855). Ovarian response and ICSI outcomes were compared among the groups. Main results and the role of chance In POR patients, significantly higher fertilization rate (68.3% ± 2.5 vs. 78.6% ± 3.7, p = 0.023), blastocyst development rate (22.5% ± 7.2 vs. 44.7% ± 6.2, p = 0.022) and implantation rate (17.6% ± 59.1 vs. 20.2% ± 43.2, p &amp;lt; 0.001) were observed in Group LH-mid, even though the amount of LH used in these patients was not significant different from that used in Group LH-mid from patients with normal response to COS (1062.35 IU ± 54.33 vs. 925.81 IU ± 414.41, p: 0.431, respectively). For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were observed in Group LH-mid compared to Group LH-start (33.0% ± 31.9 vs. 40.8% ± 32.6, p = 0.012, and 28.8% ± 30.4 vs 38.5% ± 32.3, p = 0.006, respectively). In patients aged &amp;lt; 35 years and in those with normal response to COS, similar outcomes were obtained irrespective of timing of LH administration. Limitations, reasons for caution The limitations included the retrospective design and limited sample size in subpopulations. In addition, the reduced clinical outcomes related to POR patients may hamper the true estimation of the differences between the stimulation groups in terms of pregnancy and miscarriage rates. Wider implications of the findings: In POR patients, mid-follicular phase LH supplementation starting with 150 IU daily doses, may rescue the ongoing cycle by compensating an initial slow response, and balancing the deprivation of endogenous LH in GnRH antagonist cycles, with no need of expending more gonadotropin compared to patients with normal response to COS. Trial registration number Not applicable