Luteal Phase Length Research Articles

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.

Agreement Between the 2- and 3-Step Methods for Identifying Subtle Menstrual Disturbances.

To investigate the agreement between the 2- and 3-step methods for the detection of SMDs. Menstrual cycles (MCs, 98) of 59 athletes were assessed using the 2- and 3-step methods. Regular-length MCs (ie,≥21 and ≤35d) were classified as either having no SMD (luteal phase length ≥10d, midluteal progesterone concentration ≥16nmol·L-1, and being ovulatory) or having an SMD (eg,short luteal phase [<10d], inadequate luteal phase [midluteal progesterone concentration <16nmol·L-1], or being anovulatory). Method agreement was assessed using theMcNemar test and Cohen kappa (κ). Substantial agreement was observed between methods (κ = .72; 95% CI, .53-.91), but the 2-step method did not detect all MCs with an SMD, resulting in evidence of systematic bias (χ2 = 5.14; P = .023). The 2-step method detected 61.1% of MCs that had an SMD ([51.4, 70.8]), as verified using the 3-step method, and correctly identified 100% of MCs without an SMD. MCs classified as being disturbed using the 2-step method could be considered valid evidence of SMDs. However, MCs classified without SMDs do not definitively confirm their absence, due to the proven underdetection via the 2-step method.

Experiences of women living with Polycystic Ovary Syndrome: A pilot case-control, single-cycle, daily Menstrual Cycle Diary study during the SARS-CoV-2 pandemic.

Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19-35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21-35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater "outside stress" in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with age- and BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.

Using Hormone Data and Age to Pinpoint Cycle Day within the Menstrual Cycle.

Background and Objectives: Menstrual cycle tracking is essential for reproductive health and overall well-being. However, there is still an over-reliance on estimations that standard cycles are 28 days long, divided evenly between the follicular and luteal phases. Due to the variability of cycle length and cycle phase lengths, common methods of identifying where an individual is in their cycle are often inaccurate. This study used daily hormone monitoring obtained through a remote hormone-monitoring platform to evaluate hormone levels across a menstrual cycle to identify nuances in the follicular and luteal phases in individuals of different age groups. Materials and Methods: This study used a remote fertility testing system that quantitatively tracks luteinizing hormone (LH) and pregnanediol-3-glucuronide (PdG) through urine tests read by an AI-powered smartphone app. The study analyzed cycle data from 1233 users with a total of 4123 evaluated cycles. Daily levels for LH and PdG were monitored across multiple cycles. Results: This study determined that calculated cycle lengths tended to be shorter than user-reported cycle lengths. Significant differences were observed in cycle phase lengths between age groups, indicating that follicular phase length declines with age while luteal phase length increases. Finally, the study found that if an individual's age, first cycle day, and current hormone levels are known, population-level hormone data can be used to pinpoint which cycle phase and cycle day they are in with 95% confidence. Conclusions: At-home hormone monitoring technologies can allow patients and clinicians to track their cycles with greater precision than when relying on textbook estimations. The study's findings have implications for fertility planning, clinical management, and general health monitoring. Prior to this study, no standard existed for pinpointing where a person was in their cycle through only one measure of LH and PdG. These findings have the potential to fill significant gaps within reproductive healthcare and beyond.

Distribution of the follicular and luteal phase lengths and their age-dependent changes in Japanese women: A large population study.

The current definition of menstrual cycle length in a Japanese woman is different from those of WHO definition, and the original data are outdated. We aimed to calculate the distribution of follicular and luteal phases length in modern Japanese women with various menstrual cycles. This study determined the lengths of the follicular and luteal phases of Japanese women using basal body temperature data collected via a smartphone application from 2015 to 2019, and the data were analyzed using the Sensiplan method. Over 9 million temperature readings from more than 80 000 participants were analyzed. The mean duration of the low-temperature (follicular) phase averaged 17.1 days and was shorter among participants aged 40-49 years. The mean duration of the high-temperature (luteal) phase was 11.8 days. The variance and maximum-minimum difference of the length of the low temperature period were significant in women under 35 years old than women aged more than 35 years. The shortening of the follicular phase in women aged 40-49 years implied a relationship with the rapid decline of ovarian reserve in these women, and the age 35 years old was turning point of ovulatory function.

Endocrine correlates of female reproductive activity in the roan antelope (Hippotragus equinus)

AbstractAlthough ovarian endocrine activity has been described in most members of the tribe Hippotragini, little is known about the reproductive endocrine correlates of the roan antelope (Hippotragus equinus), an endangered antelope species of southern Africa. This study characterised the endocrine pattern of the reproductive activity (oestrous cycle, pregnancy and post‐partum period) in the female roan antelope by monitoring faecal progestogen metabolite (fPM) concentrations and oestrogen metabolite (fEM) concentrations for cyclicity and observing reproductive behaviours. The study was carried out over the course of 12 months. At the beginning of this study, all 18 focal females (nulliparous, primiparous and multiparous) were monitored for cyclicity (for between 3 and 4 months). Following observed copulation, pregnancy in multiparous females (n = 10) was subsequently monitored until parturition and 21 days post‐partum. Individual faecal samples were collected three times per week during the presumed period of cyclicity, twice per week during pregnancy and daily for 21 days post‐partum. Mating births, courtship events, and copulations were recorded when observed. In eight of the 18 females monitored, the patterns of fPM and fEM concentrations indicated oestrous cycle lengths (n = 10) of approximately 30.8 ± 2.1 days. The determined lengths of luteal and follicular phases were approximately 15.8 ± 1.5 days and 14.6 ± 2.1 respectively. Pregnancy was marked by a pronounced increase in fPM concentrations until parturition, and lasted approximately 280.4 ± 4.8 days; whereas the intercalving period ranged between 306 and 380 days (n = 9; mean: 333.2 ± 7.4 days). Twenty‐one day after parturition, 78% of the focal females (n = 5) did not show a resumption of the ovarian activity. This study demonstrated that monitoring faecal reproductive hormone metabolite patterns is a valuable approach for estimating ovarian activity in roan antelope and may be used to assist respective conservation breeding programmes by improving management practices.

Systemic inflammation and menstrual cycle length in a prospective cohort study

Local inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt normal follicular dynamics. This study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length. This study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for <3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. Main outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with <1 mg/L, a C-reactive protein level >10 mg/L was associated with >3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67-8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of >10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23-3.09) days longer and with >2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05-4.74). There is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.

P-637 Evaluation of a digitally integrated ovulation prediction kit with proof of ovulation – a pilot study

Abstract Study question Is a digital ovulation prediction kit (OPK) with integrated progesterone measurements a useful tool in predicting and proving ovulation? Summary answer The digitally integrated OPK with progesterone integration may be a helpful tool for couples to identify the woman’s fertile window and detect anovulation. What is known already Apart from detecting the coming fertile window (i.e. the period of the highest probability of conception during the menstrual cycle, including the 5 days previous to and the day of ovulation itself), knowledge whether the likely ovulation indeed occurs, is crucial for achieving pregnancy. As women’s hormone profiles show intra- and interindividual variations, an individual prediction of the fertile window is a promising approach for couples, particularly in early premature ovarian insufficiency and perimenopause. Information whether the presumed ovulation has actually happened is not provided by most cycle apps. Study design, size, duration Healthy women, aged 21 to 44 years, who had not been taking hormonal contraceptives for at least three months were recruited via social media, paper postings and hand-outs. Women with infertility for more than 24 months were excluded. Up to three cycles were measured in every woman in case of a lacking pregnancy. Participants/materials, setting, methods Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) in first morning urine were gaged via lateral flow immunoassay test strips (LFIA) (RunBio Biotechnology Ltd.). Three algorithms of the smartphone application Pearl Fertility (iOS 1.0.3-1.0.5, Colorimetrix GmbH) were applied to predict the day of ovulation. Photographic visual control of the LH test strips, vaginal ultrasound close to the predicted ovulation and progesterone (PdG LFIA) were used to confirm ovulation, human chorionic gonadotropin (HCG LIFA) to confirm pregnancy. Main results and the role of chance 36 cycles of 19 women recruited for this pilot study were started. 6 participants dropped out or were excluded, leaving 25 evaluable cycles in 13 healthy women, average age 37 years (range 30 to 44), who had not been taking hormonal contraceptives for at least three months. 76 % of the analysable cycles had corresponding prediction of ovulation by algorithm and by visual control of the measured maximum value of LH (OVV). OVV corresponded with the day of ovulation determined retrospectively by length of luteal phase in 75 % (Bland-Altman plot (acceptable deviation Δ≤|2| days)). Prediction of ovulation differed by 2.12±3.13 days (mean±SD) between OVV and prospective cycle-length-based data (Wilcoxon signed-rank test (p &amp;lt; 0,05)). The PdG LIFA suggested ovulation in 84 % of the cycles with presumed ovulation by postovulatory PdG measurement. 6 of the participating women got pregnant during the study. Analysis of cumulative rate of pregnancy with 95 % confidence interval resulted in 25±21 %, 40±19 % and 40±17 % within the first, second and third cycle. Limitations, reasons for caution In order to make valid statements about the benefit of digitally integrated OPKs, further research with a larger population is needed. Perimenopausal women and patients with irregular cycles may specifically benefit from individual self-monitoring. Wider implications of the findings The knowledge of the fertile window is expected to help fertile couples to achieve pregnancy and proof of ovulation or anovulation may detect infertility due to anovulation sooner, thereby reducing the interval until diagnosis and treatment. Trial registration number 'not applicable'

Menstrual Cycle Parameters Are Not Significantly Different After COVID-19 Vaccination.

Background: Some studies have suggested minor changes in the menstrual cycle after COVID-19 vaccination, but more detailed analyses of the menstrual cycle are needed to evaluate more specific changes in the menstrual cycle that are not affected by survey-based recall bias. Materials and Methods: Using a pretest-post-test quasi-experimental evaluation of menstrual cycle parameters before and after COVID-19 vaccination, we conducted an anonymous online survey of two groups of North American women who prospectively monitor their menstrual cycle parameters daily including bleeding patterns, urinary hormone levels using the ClearBlue Fertility Monitor, or cervical mucus observations. The primary outcome measures were cycle length, length of menses, menstrual volume, estimated day of ovulation (EDO), luteal phase length, and signs of ovulation. Perceived (subjective) menstrual cycle changes and stressors were also evaluated in this study as secondary outcome measures. Results: Of the 279 women who initiated the survey, 76 met the inclusion criteria and provided 588 cycles for analysis (227 pre-vaccine cycles, 145 vaccine cycles, 216 post-vaccine cycles). Although 22% of women subjectively identified changes in their menstrual cycle, there were no significant differences in menstrual cycle parameters (cycle length, length of menses, EOD, and luteal phase length) between the pre-vaccine, vaccine, and post-vaccine cycles. Conclusions: COVID-19 vaccines were not associated with significant changes in menstrual cycle parameters. Perceived changes by an individual woman must be compared with statistical changes to avoid confirmation bias.

A one-year observational cohort study of menstrual cramps and ovulation in healthy, normally ovulating women

This is a prospective, observational community cohort study with the objective of investigating menstrual cramp occurrence related to ovulatory characteristics. Women reported cramp intensity on daily Menstrual Cycle Diary© records over one year. Ovulation and luteal phase lengths were assessed by validated Quantitative Basal Temperature© (QBT) analysis. Healthy, normal-weight, non-smoking community dwelling premenopausal women ages 21–41 years with two consecutive, normally ovulatory, normal-length menstrual cycles were enrolled. All 53 women, with 13.6 ± 2.8 cycles per woman, reported at least one cramp episode of median intensity 1.5 [0–4 scale; range 1.0–3.5], and 2.2 days’ [range 1.0–10.2] duration. Within the 49 women who experienced all ovulatory cycle types (normal, short luteal length [SLL < 10 days] and anovulatory), median cramp intensity was greater in normal-length cycles having subclinical ovulatory disturbances (SLL and anovulatory; median 1.4 [range 0.0–2.8]) than in normally ovulatory cycles (median 1.2 [range 0.0–2.3]) (P = 0.023). Cramp Scores did not differ by ovulatory status within the 19 women having both normally ovulatory and anovulatory cycles (P = 0.222). Within-woman 1-year Cramp Scores were not different in anovulatory and normally ovulatory menstrual cycles but were more intense with ovulatory disturbances.

Luteal phase length, endometrial edema, and behavior differentiate post-ovulatory events in a giant panda (Ailuropoda melanoleuca).

Despite decades of reproductive research on the giant panda (Ailuropoda melanoleuca), the post-ovulatory phase continues to confound zoologists in conservation and breeding centers around the world, often resulting in significant investments of time and resources without reproductive success. The purpose of this project was to document and compare post-ovulatory characteristics during a non-productive and productive breeding in the same individual in consecutive years. A multidisciplinary approach was used to monitor the visiting female giant panda at the Toronto Zoo through the luteal phase of her first two full reproductive cycles in 2014 and 2015. Monitoring occurred via urine-endocrine analysis, weekly ultrasound examinations, and continuous behavioral observations. The 2014 reproductive cycle consisted of a pseudopregnancy, characterized by an extended luteal phase (241 days), the identification of endometrial edema and folding during ultrasound examinations, and a lack of strong association between behavior patterns and urinary progestagen secretion. The 2015 reproductive cycle included increased feeding time through the primary progestagen rise compared to the previous year, followed by simultaneous decrease in appetite and increases in inactivity, resting, sitting upright, and pre-partum-associated behaviors. These changes began 25 days before the birth of twins on Day 153 post-ovulation. Both fetuses were detected via ultrasound 15 days pre-partum. These results suggest that an absence of pre-partum behaviors, ultrasound evidence of endometrial edema without a fetus, and an extended luteal phase may be indicative of pseudopregnancy in giant pandas. Simultaneous monitoring of morphology, behavior, and urinary-endocrine profiles showed clear differences between successful and unsuccessful reproductive years.

Single-step genome-wide association study uncovers known and novel candidate genomic regions for endocrine and classical fertility traits in Swedish Red and Holstein dairy cows

• In this study, the novel endocrine and classical fertility traits of Swedish dairy herds were evaluated using in-line milk progesterone profiles in ssGWAS approach. • The genomic regions associated with the endocrine and classical traits were identified. • A total of 20 QTLs, of which 18 of them are novel, were detected. The novel QTL regions embedded candidate genes ( ATG7, GPI, GJA1, PPP3CA, ECT2, ARHGAP20, PHLDB1, CACNA1D, CCNE1, CDH13, PLD1, FBN2, KIF3A, FGF12, KCNMB2, MAN1A1, KCNN2, SMAD6, MAPK8IP1, PHF21A, LPXN, MMRN1, KCNIP4, NID2, PCDHGA8, GRIA1, PCDHGB4, PHLDB2, STXBP5L, PTPRR, SRGAP1, SNX27, SPTA1, S100A10, TBC1D20 and ITCH ) that are associated with endocrine and classical fertility traits. • The candidate QTL regions provide insights into the genetic basis of endocrine and classical fertility in SR and Holstein dairy breeds. In a study aiming to identify candidate genomic regions associated with endocrine and classical fertility traits in Swedish Red (SR) and Holstein cows, data on 3955 lactations in 1164 SR and 1672 Holstein cows were examined. The dataset comprised milk progesterone (P4) levels ( n = 341,212) in 14 Swedish herds, automatically collected and analyzed in-line using the DeLaval Herd Navigator™. Endocrine traits studied were: days from calving to commencement of luteal activity (C-LA), first luteal phase length (LPL), length of first inter-luteal interval, length of first inter-ovulatory interval (IOI), luteal activity during the first 60 DIM, and proportion of samples with luteal activity during the first 60 DIM. Classical fertility traits based on insemination data were also investigated, such as days from calving to last insemination and calving interval. A total of 180 SR and 312 Holstein cows were genotyped with a low-density SNP chip and imputed to 50 K. Single-step genome-wide association (ssGWAS) was used to explore candidate genomic regions associated with fertility traits. A mixed linear single-trait animal model was fitted, considering season and parity as fixed effects and animal and permanent environment as random effects. The results revealed 990 and 415 SNPs above the threshold (-log ( p -value) ≥4) for SR and Holstein cows, respectively. The breeds shared only eight SNPs significantly associated with fertility traits. Annotation analysis revealed 281 SNPs located in 241 genes. Functional enrichment analysis using DAVID tools reduced the number to 80 genes, which were mediated in various biological processes and KEGG pathways in multiple functions, including folliculogenesis, embryogenesis, uterine growth and development, immune response, and ovarian cysts. Of the 80 genes, 67 were associated with fertility traits in SR cows and 13 in Holstein. Most genes were associated with LPL and IOI in SR cows, but in Holstein the only association with an endocrine trait was with C-LA. Twenty QTL regions that embedded 40 genes were associated with fertility traits in both breeds. All the QTLs detected, except at BTA2 and BTA19 are novel QTL regions that were not reported previously. These novel QTL regions embedded the candidate genes that include ARHGAP20, PHLDB1, CACNA1D, ATG7, CCNE1, GPI, CDH13, ECT2, PLD1, FBN2, KIF3A, FGF12, KCNMB2, GJA1, MAN1A1, KCNN2, SMAD6, MAPK8IP1, PHF21A, LPXN, MMRN1, KCNIP4, NID2, PCDHGA8, GRIA1, PCDHGB4, PHLDB2, STXBP5L, PPP3CA, PTPRR, SRGAP1, SNX27, SPTA1, S100A10, TBC1D20 and ITCH. The candidate regions may help to improve genetic progress in female fertility if used in selection decisions. A challenge for future research is to determine why different regions seem relevant for different traits and breeds, and the practical implications for genomic selection.

Adiposity Alters Follicle Dynamics in Women of Reproductive Age With Regular Menstrual Cycles

Obesity increases a woman’s likelihood of experiencing adverse reproductive health outcomes, including menstrual cycle irregularity, anovulation, and luteal phase dysfunction. Despite a heightened risk of reproductive dysfunction some women with obesity display ovulatory cyclicity. The degree to which adiposity affects menstrual cycle characteristics in this population is limited to endocrine assessments; evidence supports decreased luteinizing hormone pulse amplitude and reduced luteal phase progesterone. However, these endocrine disruptions have not been linked to alterations in follicular events. The objectives of the present analysis were to evaluate longitudinal changes in follicle size populations and growth kinetics of selectable follicles (6-9mm) and identify endocrine abnormalities associated with obesity in regular cycles. 14 non-obese women (BMI <30 kg/m2) and 15 obese women (BMI≥ 30 kg/m2) with regular cycles 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 ≥2 mm 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. Diagnostic, morphologic, and endocrine features were compared across groups using parametric and non-parametric t-tests (i.e. cross-sectional features) and mixed models (i.e. longitudinal features). Non-obese and obese women with regular cycles showed similar IOI, follicular phase, and luteal phase lengths. The mean number of recruitment events, maximum dominant follicle diameter, and the growth rates of ovulatory follicles over time did not differ between groups, despite confirmation of compromised mean luteal progesterone production (8.23 ng/mL vs. 14.75 ng/mL, p=0.047) and decreased mean luteal FSH levels in women with obesity (2.33 mIU/mL vs. 5.83 mIU/mL, p=0.040). Over the IOI women with obesity showed an increased proportion of 2-5 mm follicles (β=5.3%; p<0.05) and a decreased proportion of 6-9mm follicles (β=-5.0%; p=0.05) versus non-obese women consistent with fewer follicles transitioning from the 2-5 mm pool to the selectable stage. This is the first comparison of follicle dynamics between non-obese and obese women with regular ovulatory cycles. These data suggest that a smaller pool of selectable follicles is present in women with obesity and may result in suboptimal follicle development luteal function. Future studies are needed to understand the impact of altered follicle populations and luteal hormone dynamics on endometrial receptivity and fertility/fecundity.

Diagnosis and treatment of luteal phase deficiency: a committee opinion

Luteal phase deficiency (LPD) is a clinical diagnosis associated with an abnormal luteal phase length of ≤10 days. Potential etiologies of LPD include inadequate progesterone duration, inadequate progesterone levels, or endometrial progesterone resistance. LPD has not only been described in association with medical conditions but also in fertile, normally menstruating women. Although progesterone is important for the process of implantation and early embryonic development, LPD has not been proven to be an independent entity causing infertility or recurrent pregnancy loss. Controversy exists regarding the multiple proposed measures for diagnosing LPD and, assuming it can be diagnosed accurately, whether treatment improves outcomes. This document replaces the document entitled "Current clinical irrelevance of luteal phase deficiency: a committee opinion," last published in 2015 (Fertil Steril 2015;103:e27-e32).

Ovarian Reserve Biomarkers and Menstrual Cycle Length in a Prospective Cohort Study.

While age-related changes in menstrual cycle length are well known, it is unclear whether anti-Müllerian (AMH) or other ovarian reserve biomarkers have a direct association with cycle length. To determine the association between biomarkers of ovarian reserve and menstrual cycle length. Secondary analysis using data from time to conceive (TTC), a prospective time to pregnancy cohort study. The age-independent association between cycle length and biomarkers of ovarian reserve was analyzed using linear mixed and marginal models. Study participants were TTC-enrolled women aged 30-44 years with no history of infertility who were attempting to conceive for <3 months were enrolled. Serum AMH, follicle-stimulating hormone, and inhibin B levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. The primary outcome was menstrual cycle length; follicular and luteal phase lengths were secondary outcomes. Multivariable analysis included 1880 cycles from 632 women. Compared with AMH levels of 1.6 to 3.4 ng/mL, women with AMH <1.6 ng/mL had cycles and follicular phases that were 0.98 (95% CI -1.46, -0.50) and 1.58 days shorter (95% CI -2.53, -0.63), respectively, while women with AMH >8 ng/mL had cycles that were 2.15 days longer (95% CI 1.46, 2.83), follicular phases that were 2 days longer (95% CI 0.77, 3.24), and luteal phases that were 1.80 days longer (95% CI 0.71, 2.88). Increasing AMH levels are associated with longer menstrual cycles due to both a lengthening of the follicular and the luteal phase independent of age.

Low-dose aspirin in reproductive health: effects on menstrual cycle characteristics

To estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles. Secondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses. University medical centers. A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur. Randomized allocation to LDA versus placebo. Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short (<25th percentile: <27 days) and long (>75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant. There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups. Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo. NCT00467363.

Pregnancy rates and luteal phase characteristics of bovine embryo recipients treated with flunixin meglumine

ABSTRACT The aim of this study was to evaluate the effects of flunixin meglumine administration on pregnancy rates and luteal phase characteristics in bovine embryo recipients at the moment of embryo transfer. In experiment 1, in vitro produced embryos were transferred to 184 females divided as control and treated group (recipients treated with 1.1mg/kg flunixin meglumine). In experiment 2, 22 females were divided as control group; group 2 (animals submitted to a reproductive tract manipulation similar to an embryo transfer on the 7th day after estrous); and group 3 (females submitted to a manipulation and treatment with 1.1mg/kg flunixin meglumine). In experiment 1 no difference was observed between control and treated groups (40.2% and 44.6%, respectively) for pregnancy rates. In experiment 2 no difference was observed on the length of luteal phase between groups, however, animals in group 2 presented lower plasma progesterone concentrations than the control group and group 3. Therefore, we concluded that although the administration of flunixin meglumine at the moment of embryo transfer inhibited the reduction plasma progesterone concentrations, it was not effective in increasing pregnancy rates of bovine recipients.

Menstrual bleeding, cycle length, and follicular and luteal phase lengths in women without known subfertility: A pooled analysis of three cohorts.

There is variability between women for days of menstrual bleeding, cycle lengths, follicular phase lengths, and luteal phase lengths, related to age and parity. To describe total cycle length; anovulatory cycles; follicular and luteal phase lengths; and days and intensity of menstrual and non-menstrual bleeding in women without known subfertility over the course of 1year. 581 women (3,324 cycles) with no known subfertility (18-40years of age) were followed for up to 1year. Women recorded vaginal bleeding and mucus discharge daily. We used the peak day of cervical mucus as the estimated day of ovulation and the last day of the follicular phase. We used generalised linear mixed models stratified by age and parity to describe menstrual cycle parameters. The majority of women were <30years of age (74.5%), non-Hispanic White (88.6%), and nulliparous (70.4%). The mean menses length was 6.2 (1.5) days, median 6; cycle length 30.3 (6.7) days, median 29; follicular phase length 18.5 (6.5) days, median 17; and luteal phase length 11.7 (2.8) days, median 12. Nulliparous women aged ≥30years vs nulliparous women aged <30 had shorter cycles (29.2days, 95% confidence interval (CI) 27.8, 30.7 vs 31.5days, 95% CI 30.8, 32.2) and shorter follicular phases (17.6days, 95% CI 16.2, 18.9 vs 19.6days, 95% CI 18.9, 20.2). Among all women, within-woman differences between the longest and shortest menses length >3days, total cycle length >7days, follicular phase >7days, and luteal phase >3days were found in 11.6%, 43.0%, 41.7%, and 58.8% of women, respectively. Our findings confirm variability between women of menstrual cycle parameters related to age and parity, and also highlight within-woman variability in the follicular and luteal phases.

Effects of 3-nitrooxypropanol on rumen fermentation, lactational performance, and resumption of ovarian cyclicity in dairy cows

This study examined the effect of 3-nitrooxypropanol (3-NOP), a substance under investigation, on enteric methane (CH4) emission, rumen fermentation, lactational performance, sensory properties of milk, and the resumption of ovarian cyclicity in early-lactation dairy cows. Fifty-six multi- and primiparous Holstein cows, including 8 that were rumen cannulated, were used in a 15-wk randomized complete block design experiment. Cows were blocked based on parity and previous lactation milk yield (MY) or predicted MY, and within each block were randomly assigned to one of 2 treatments: (1) control (CON), administered no 3-NOP, or (2) 3-NOP applied at 60 mg/kg of feed dry matter (3-NOP). Enteric CH4 emission was measured during experimental wk 2, 6, 9, and 15, using the GreenFeed system. Dry matter intake (DMI) and MY data were collected daily throughout the experiment, and milk composition samples were collected 7 times during the experiment. Milk samples were collected from 14 to 60 (±2) d after calving, 3 d per week, and assayed for progesterone concentration to determine resumption of ovarian activity. Compared with CON, 3-NOP decreased daily CH4 emission by 26%, CH4 yield (CH4 per kg of DMI) by 21%, and CH4 emission intensity [CH4 per kg of MY or energy-corrected milk (ECM)] by 25%. Enteric emission of carbon dioxide was decreased by 5%, and hydrogen emission was increased 48-fold by 3-NOP. Inclusion of 3-NOP decreased concentration of total volatile fatty acids (by 9.3%) and acetate but increased butyrate molar proportion, ethanol, and formate concentrations in ruminal fluid. Dry matter intake was lower for 3-NOP compared with CON, but DMI expressed as a percentage of body weight was not different between treatments. Treatment had no effect on milk and ECM, body weight change, or body condition score. Milk composition and milk fat and protein yields were not affected by treatment, except that concentrations of short-chain fatty acids in milk were increased by 3-NOP. Nutrient digestibility and blood metabolites and hormones were not affected by 3-NOP, except that insulin was decreased by 3-NOP. There was no effect of 3-NOP on postpartum resumption of ovarian activity, including days to first and second luteal phases, length of first and second luteal phases, and interval from first to second luteal phase. Sensory properties of milk from cows fed 3-NOP and cheese made from that milk were not affected by treatment. In this experiment, 3-NOP decreased daily enteric CH4 emission, emission yield, and emission intensity, improved feed efficiency, and did not affect lactational performance or onset of ovarian activity in early-lactation dairy cows.

Genetic parameters of endocrine fertility traits based on in-line milk progesterone profiles in Swedish Red and Holstein dairy cows

Evaluating fertility traits based on endocrine progesterone profiles is becoming a promising option to improve dairy cow fertility. Several studies have been conducted on endocrine fertility traits, mainly in the Holstein breed. In this study, focusing also on the Swedish Red (SR) breed, genetic parameters were estimated for classical and endocrine fertility traits, the latter based on in-line milk progesterone records obtained for 14 Swedish herds using DeLaval Herd Navigator (DeLaval International, Tumba, Sweden). A total of 210,403 observations from 3,437 lactations of 1,107 SR and 1,538 Holstein cows were used. Mixed linear animal models were used for estimation of genetic parameters. Least squares means analysis showed that Holstein cows had a 2.5-d-shorter interval from calving to commencement of luteal activity (C-LA) and longer length of first inter-ovulatory interval (IOI) than SR cows. The highest mean interval for C-LA, IOI, and first luteal phase length (LPL) was observed in the fourth parity. The incidence of short (<18 d), normal, (18-24 d), and long (>24 d) IOI was 29.3, 40.7, and 30%, respectively. Genetic analysis indicated moderate heritability (h2) for C-LA (h2 = 0.24), luteal activity during the first 60 d in milk (LA60, h2 = 0.15), proportion of samples with luteal activity (PLA, h2 = 0.13), and calving to first heat (CFH, h2 = 0.18), and low heritability estimates for LPL (h2 = 0.08) and IOI (h2 = 0.03) in the combined data set for both breeds. Similar heritability estimates were obtained for each breed separately except for IOI and LPL in SR cows, for which heritability was estimated to be zero. Swedish Red cows had 0.01 to 0.06 higher heritability estimates for C-LA, LA60, and PLA than did Holstein cows. Calving interval had moderate heritability among the classical traits for Holstein and the combined data set, but h2 was zero for SR. Commencement of luteal activity had a strong genetic correlation with LA60 (mean ± SE; -0.88 ± 0.06), PLA (-0.72 ± 0.11), and CFH (0.90 ± 0.04). Similarly, CFH had a strong genetic correlation with IOI (0.98 ± 0.20). Number of inseminations per series showed a weak genetic correlation with all endocrine traits except IOI. Overall, endocrine traits had higher heritability estimates than classical traits in both breeds, and may have a better potential to explain the actual reproductive status of dairy cows than classical traits. This might favor inclusion of some endocrine fertility traits-especially those related to commencement of luteal activity-as selection criteria and breeding goal traits if recording becomes more common in herds. Further studies on genetic and genomic evaluations for endocrine fertility traits may help to provide firm conclusions. A prerequisite is that the data from automatic devices be made available to recording and breeding organizations in the future and included in a central database.