Longer Follicular Phase Research Articles

Quantitative Hormone Analysis Reveals Sources of Variability in the Menstrual Cycle

Although the fluctuations of hormones over the menstrual cycle are well recognized, this study investigated the variability in these patterns for individual women. This study examined a set of daily blood hormone results from an underlying data set of previous research. Hormones included follicle-stimulating hormone (FSH), luteinizing hormone, progesterone, and estradiol taken over one menstrual cycle in 20 women of reproductive age (age 20–36 years), with ultrasound-confirmed ovulation. Although every woman’s profile of hormone changes was consistent with the expected physiological sequence of events, there was notable variability in the timing and peak levels. Variability in the length of the follicular phase was greater than in the length of the luteal phase, with the greater part of the variability in the cycle length being explained by variability in the follicular phase. Lower levels of FSH at the beginning of the cycle were associated with a longer follicular phase. Variability in the timing of events around ovulation was relatively consistent across all women. Variability in the length of the luteal phase was associated with the duration of elevated levels of progesterone. Differences were seen in the extent to which FSH increased at the end of the cycle. This study suggests the variability of the first part of the follicular phase may be due to initial FSH changes. Understanding the variability of menstrual cycle hormones is relevant for all women. Identifying subclinical ovulatory disturbances and variability is important to understand female health, across different populations including menstruating women and female athletes.

Post-thaw culture has no beneficial effect on frozen embryos transfer outcomes comparing to same embryonal age non-cultured frozen-thawed embryos

Purpose To assess the impact of post-thawing embryo culture on frozen embryo transfer (FET) outcomes. Methods A retrospective cohort study including 678 consecutive FET cycles performed between the years 2004 and 2017 was conducted. Patients older than 45 years old were excluded. FET cycles were stratified as follows: (1) two-day (2d) embryos thawed and cultured to three-day (3d) versus 3d embryos thawed and transferred; (2) 2d or 3d embryos thawed and cultured to blastocysts versus blastocysts thawed and transferred. A p-value <.05 was considered statistically significant. Results Maternal age, BMI, smoking, and basal FSH of the 2d and 3d cultured embryo group (n = 110) and the 3d non-cultured embryo group (n = 189) were comparable. Endometrium preparation protocols and the achieved endometrial thickness did not differ between groups. Pregnancy rate, implantation rate, clinical pregnancy, live birth rate, abortions, multiple pregnancies, perinatal outcomes, and birth weight were comparable. The 2d and 3d embryos cultured to blastocyst (n = 41) compared to non-cultured blastocyst (n = 338) showed that the non-cultured blastocyst patients had higher smoking rates and longer follicular phase. Endometrial thickness was comparable. The 2d and 3d embryos cultured to blastocyst stage had higher multiple pregnancies rate compared to the blastocyst non-cultured group, whereas pregnancy rate, implantation rate, live birth rate, miscarriages, perinatal outcomes, and birth weight were comparable. Conclusion We could not demonstrate that the post-thaw culture had a significant impact on the outcome of FET cycles.

Differences in ovarian hormones in relation to parity and time since last birth

To examine ovarian function in relation to parity and time since last birth. Cross-sectional study. Health-care program in California. 346 naturally cycling women, aged 18 to 39 years. None. Mean follicular urinary estradiol metabolite concentration (E1C) (cycle days -8 to -1), mean luteal progesterone metabolite concentration (PdG) (days 0 to +10), and cycle phase lengths in ovulatory cycles. After the women had collected daily urine samples for up to eight menstrual cycles, we measured the E1C and PdG using enzyme-linked immunoassay. The cycle phase lengths were calculated from the hormone profiles and daily diaries. Women who had given birth within the previous 3 years had lower E1C than the nulliparous women and women who last given birth >3 years earlier. Among the parous women, E1C was positively associated with the time since last birth. Women who last gave birth >3 years earlier had longer follicular phases than the nulliparous women. There were no associations between parity and PdG or luteal phase length. Our cross-sectional data suggest that ovarian function differs in nulliparous and parous women and is positively associated with the time since last birth. Longitudinal research is needed to explore within-woman changes in ovarian function prepartum and postpartum.

Menstrual cycle characteristics and reproductive hormone levels in women exposed to atrazine in drinking water

Atrazine is the most commonly used herbicide in the U.S. and a wide-spread groundwater contaminant. Epidemiologic and laboratory evidence exists that atrazine disrupts reproductive health and hormone secretion. We examined the relationship between exposure to atrazine in drinking water and menstrual cycle function including reproductive hormone levels.Women 18–40 years old residing in agricultural communities where atrazine is used extensively (Illinois) and sparingly (Vermont) answered a questionnaire (n=102), maintained menstrual cycle diaries (n=67), and provided daily urine samples for analyses of luteinizing hormone (LH), and estradiol and progesterone metabolites (n=35). Markers of exposures included state of residence, atrazine and chlorotriazine concentrations in tap water, municipal water and urine, and estimated dose from water consumption.Women who lived in Illinois were more likely to report menstrual cycle length irregularity (odds ratio (OR)=4.69; 95% confidence interval (CI): 1.58–13.95) and more than 6 weeks between periods (OR=6.16; 95% CI: 1.29–29.38) than those who lived in Vermont. Consumption of >2 cups of unfiltered Illinois water daily was associated with increased risk of irregular periods (OR=5.73; 95% CI: 1.58–20.77). Estimated “dose” of atrazine and chlorotriazine from tap water was inversely related to mean mid-luteal estradiol metabolite. Atrazine “dose” from municipal concentrations was directly related to follicular phase length and inversely related to mean mid-luteal progesterone metabolite levels.We present preliminary evidence that atrazine exposure, at levels below the US EPA MCL, is associated with increased menstrual cycle irregularity, longer follicular phases, and decreased levels of menstrual cycle endocrine biomarkers of infertile ovulatory cycles.

Lifestyle and reproductive factors associated with follicular phase length.

Variability in menstrual cycle length, largely determined by variation in follicular phase length, is related to several health outcomes, yet the causes of this variability are incompletely understood. We sought to identify characteristics associated with follicular phase length. We used the North Carolina Early Pregnancy Study to describe factors correlated with timing of ovulation (follicular phase length). Women collected daily urine specimens and recorded vaginal bleeding. Specimens were assayed for estrone 3-glucuronide and pregnanediol 3-glucuronide, which in turn were used to estimate the day of ovulation. All other variables were assessed through interview. Associations with follicular phase length were evaluated using a multiple regression model. We determined follicular phase length for the first cycles of 201 women. Women with a history of miscarriage tended to have shorter follicular phases (2.2 days). Longer duration of oral contraceptive (OC) use and recent OC use (in the last 90 days) were both correlated with longer follicular phase. Occasional marijuana users (up to three times in the last 3 months) had a longer follicular phase than nonusers (3.5 days); the follicular phase in frequent users (more than three times) was almost 2 days longer than that of nonusers. The association between marijuana use and longer follicular phase is consistent with prior rhesus monkey research that shows ovulatory delay or inhibition.

Menstrual cycle lengths and bone mineral density: a cross-sectional, population-based study in rural Chinese women ages 30–49 years

The menstrual cycle involves periodic fluctuations in estrogen and progesterone levels. Longer cycles have been associated with longer follicular phase, delayed estrogen peak and a lower mean oestradiol level of the entire cycle. We hypothesized that prolonged menstrual cycle length is associated with decreased bone mineral density (BMD) in a population of pre- and perimenopausal women. This population-based cross-sectional study was conducted in rural Anhui province, China. It includes 4,771 women, aged 30 to 49 years, who did not smoke or drink alcohol, and did not use oral contraceptives or breastfeed during the previous year. Dual-energy X-ray absorptionometry (DEXA) BMD measurements were taken at four skeletal sites: whole body, total hip, femoral neck and lumbar spine. Menstrual cycle characteristics (polymenorrhea, short normal, long normal, oligomenorrhea, 90-day amenorrhea, irregular cycle) in the prior year were assessed by questionnaire. Prolonged menstrual cycle was consistently associated with decreased BMD at whole body, total hip, and femoral neck in both age 30-39, and age 40-49 stratum (p(trend)<0.05). Prolonged menstrual cycle was also associated with decreased lumbar spine BMD for women aged 40-49 (p(trend)<0.05). Among women with normal cycles aged 30-39, menstrual cycle length in the previous year was inversely associated with whole-body BMD (p<0.05). Women with 90-day amenorrhea had significantly lower mean total hip and femoral neck BMD relative to women with short normal cycles in the 30-39 age group; and had significantly lower whole body and total hip BMD relative to short normal cycles in the 40-49 age group. BMD in polymenorrheic women did not differ from BMD in women with short normal cycles at any of the skeletal sites. We conclude that prolonged menstrual cycle length is associated with decreased BMD in pre- and perimenopausal women in this population.

Phytoestrogens and reproductive biology.

Phytoestrogens are naturally occurring plant substances that can either mimic or antagonize the action of endogenous estrogens. This is because of the similarity of the functional structure of phytoestrogens and endogenous estrogens. In premenopausal women, phytoestrogen intake might induce a decrease in luteinizing hormone, follicle-stimulating hormone and estradiol (E2), which are associated with a longer follicular phase. The circulating transport protein, sex hormone-binding globulin, is increased, resulting in less cellular availability of E2. Phytoestrogens inhibit the activities of E2 synthetic enzymes through adenylate cyclase and tyrosine kinase cascades. This might decrease of risk of hormone dependent cancers. A phytoestrogen-rich diet might reproduce normal body composition, affecting the course of polycystic ovary syndrome (PCOS). Some herbs used in traditional Japanese medicine contain phytoestrogens that influence endogenous hormone levels to directly regulate the pituitary-ovarian system, in particular, the chemotactic effects on ovaries. (Reprod Med Biol 2005; 4: 225 -229).

Body Size and Ethnicity Are Associated With Menstrual Cycle Alterations in Women in the Early Menopausal Transition: The Study of Women???s Health Across the Nation (SWAN) Daily Hormone Study

The SWAN is a multiethnic, community-based, longitudinal cohort study of 3302 women at 7 sites who initially were 42 to 52 years of age. Daily patterns of reproductive hormones have been studied in a subgroup of 848 women. A total of 833 menstrual cycles were evaluated. Urinary levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone conjugate (E1c), and pregnanediol glucuronide (Pdg) were used in algorithms to evaluate menstrual cycles for features of folliculogenesis, ovulation, and corpus luteum function. A significant rise in Pdg was taken as evidence of luteal activity (ELA), which is consistent with ovulation. A 60% decrease in the E1c to Pdg ratio indicated a luteal shift (DLT). Phase-specific lengths of cycles with ELA were estimated using the DLT as day 0, excluding day 0 from both follicular and luteal phase lengths. Hormone levels were summed over the total cycle and over the follicular and luteal phases for cycles with ELA. Participants were 43–53 years of age. Just over one third had smoked, and more than half were either overweight or obese. Just over one fourth of women were premenopausal; the rest were in the early perimenopausal phase. Approximately 81% of cycles had ELA, and these were the ones used in the following comparisons. Hispanic women had more long cycles exceeding 33 days and fewer short ones less than 22 days. Both longer and shorter cycles were most frequent in women aged 49 and older. Women whose body mass index (BMI) exceeded 25 kg/m2 had longer cycles on average than those with lower values. Early perimenopausal women were likelier than premenopausal women to have long cycles. On multivariate analysis, only age was significantly associated with total cycle length. BMI was the strongest predictor of phase lengths, larger women having longer follicular phases and shorter luteal phases. The differences remained significant on multivariate analysis. The follicular phase was significantly longer on average in early perimenopausal than in premenopausal women. Neither age nor smoking status influenced phase lengths. Hispanic women had longer luteal phases than other ethnic groups, but there were no significant ethnic differences after adjusting for BMI. Apart from E1c, daily hormone levels were highest in women whose BMI was 25 kg/m2 or less. Lower BMI correlated with higher total-cycle E1c values. Chinese and Japanese women had higher Pdg and lower E1c levels, largely because of the influence of BMI. Women over age 49 years had higher total-cycle FSH levels but lower total-cycle PdG values than did younger women. Smoking did not predict Pdg on multivariate analysis. Total-cycle FSH was higher in early perimenopausal than in premenopausal women, partly because of age differences. Total-cycle hormone levels were related to BMI in this study, and ethnicity seems to play a role independently of body size. It is not clear whether the observed differences are the result of differing rates of progress through the menopausal transition related to body size or ethnicity, or whether the differences will persist with longer follow up.

Length of the follicular phase, time of insemination, coital rate and the sex of offspring.

The penetrability of cervical mucus improves over the follicular phase. When the length of the follicular phase varies due to variation in the timing of the luteinizing hormone surge, mucus penetrability will also improve as the phase lengthens. As selection for Y spermatozoa decreases with improvements in mucus penetrability, sex ratios at conception should decline in longer follicular phases. Sex ratios should also decline as the time of insemination approaches ovulation unless hormonally-induced improvements in penetrability are reduced by the debris left by earlier inseminations.

Effects of age and non-hormonal contraception on menstrual cycle characteristics

The objective of this study was to investigate the effects of age and non-hormonal contraceptive method on menstrual cycle parameters.The menstrual cycle data were collected prospectively, and the study was cross-sectional with regard to age. The subjects were 142 women, including 14 asymptomatic volunteers and 128 women who presented to a premenstrual tension (PMT) clinic. The age range was 20-45 years. Contraceptive methods used were intrauterine device (IUD) (n = 12), tubal ligation (n = 61) and non-intrusive methods (n = 69).Daily menstrual cycle diaries were used to calculate cycle length and number of days of menstruation. Daily 24-h urine collections were used to calculate the day of the preovulatory estrogen peak.Pearson correlations found significant relationships between age and preovulatory estrogen peak day (p < 0.001) and length of cycle (p < 0.002), but not between age and length of menstruation or luteal phase. Analysis of variance was highly significant for age and contraceptive method, for both cycle length and preovulatory estrogen peak day. Non-intrusive contraception users aged 30 years and younger had significantly longer follicular phases than did women with tubal ligation (p < 0.05).It was concluded that cycle length decreases with age due to shortening of the follicular phase. Further research on whether tubal ligation affects ovulation and follicular phase length in young women is needed.

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 to 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 μl in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 μg/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination. Intranasal administration of NET had no significant effect on mean menstrual cycle length. However, other parameters were affected in a significant number of treatment cycles. The mean cervical mucus score of 13.5 in pretreatment cycle was reduced significantly in 5 and 6 volunteers in the first and second treatment cycles, respectively, and in the others it was not affected. In 10 treatment cycles the vaginal cytology was indicative of anovulation and in one each it was inconclusive and ovulatory. Since in 2 volunteers the vaginal smears during the pretreatment cycles were not indicative of ovulatory cycles, it was considered that their vagina were probably refractory to hormonal changes and were thus not considered for purposes of evaluating the effects of NET on vaginal cytology. On the basis of endocrine profile, 8 cycles showed ovulatory pattern in which progesterone levels were indistinquishable from pretreatment cycle, 5 cycles were anovulatory and the remaining 3 were deficient in progesterone and had longer follicular phase and shorter luteal phases. Ultrasonographic evidence of normal folliculogenesis and ovulation was observed in 7 cycles. Formation of follicular cysts was seen in 8 treatment cycles of which 7 were anovulatory and in one ovulation was observed in the contralateral ovary. The size of the cysts varied between 29 to 44 mm. The cysts disappeared either just before the menses in the same cycle or by the middle of post-treatment cycle. A positive correlation (r = 0.679) in the size of follicular cyst with estradiol levels was observed. In two cycles normal folliculogenesis was observed; however, the follicle did not rupture at the anticipated time. Since these two cycles had normal estradiol and progesterone levels, these were classified to have luteinized unruptured follicles. Out of 11 samples of endometrial aspirates, which could be collected during two treatment cycles, hormonal effects were seen in 10 and in one the endometrium was secretory. In 5 cycles where the aspirates could not be collected, it is possible that the endometrium was either very scanty or had undergone atrophy. These observations, therefore, provide convincing evidence that NET administered intranasally causes changes both in the reproductive endocrine parameters as well as on the end organs and that these changes are suggestive of antifertility effects.