Heart rate variability between hormone phases of the menstrual and oral contraceptive pill cycles of young women.

INTRODUCTION: The interplay between the sympathetic and parasympathetic branches of the autonomic nervous system contribute to adequate hemodynamic responses to stressors, reflected by the variation in intervals between heart beats, known as heart rate variability. The sex hormones estrogen and progesterone have been shown to affect autonomic function. The extent to which autonomic function may vary between different hormone phases of the natural menstrual cycle and how this relationship may differ in women taking oral contraceptives has yet to be fully elucidated. PURPOSE: To investigate differences in heart rate variability between the early follicular and early luteal phases of the menstrual cycle in naturally menstruating women and in oral contraceptive pill users. METHODS: Twenty-two young (22 ± 3 years), healthy women who were naturally menstruating or taking oral contraceptive pills participated in this study. Heart rate variability was measured at rest and during two sympathomimetic stressors: isometric handgrip exercise and cold pressor test. RESULTS: The proportion of successive NN intervals that differ by more than 50 ms was higher in oral contraceptive pill users during the placebo pill phase. Absolute high-frequency power was higher in the naturally menstruating women during the early luteal phase, relative to the early follicular phase. Other indices of vagal modulation were not different at rest or during sympathetic activation between hormone phases or groups. CONCLUSIONS: Vagal modulation may be increased in the early luteal menstrual cycle phase. Further,oral contraceptive use does not appear to adversely affect this modulation in young, healthy women.

Shortcomings of an unphysiological triggering of oocyte maturation using human chorionic gonadotropin.

Final maturation of follicles has, in connection with ovarian stimulation and infertility treatment, traditionally been achieved by the administration of a human chorionic gonadotropin (hCG) bolus trigger of 5,000 to 10,000 IU. This trigger serves two purposes: induce oocyte maturation; and serve as luteal phase support owing to its long half-life. It now appears that the hCG bolus trigger is unable to support both these two purposes optimally. In particular, after an hCG trigger, the early luteal phase is hormonally abnormal and different from conditions observed in the natural menstrual cycle: the timing of the initiation of hCG and progesterone rise is much faster after an hCG trigger than in a natural menstrual cycle; the maximal concentrations of hCG and progesterone considerably exceed those naturally observed; and the timing of the peak progesterone concentration after an hCG trigger is advanced several days compared with the natural cycle. Furthermore, the hCG trigger without any follicle-stimulating hormone activity may induce oocyte maturation less efficiently than the combined luteinizing hormone and follicle-stimulating hormone surge normally seen. Collectively, the endometrium is likely to be advanced after an hCG trigger, and the implantation potential is probably not optimal. The precise effect on pregnancy rates after the different progressions of hCG and progesterone concentrations during the early luteal phase has not yet been determined, but more individualized methods using more physiological approaches are likely to improve reproductive outcomes.

Response to ovulation trigger is correlated to late follicular phase progesterone levels: A hypothesis explaining reduced reproductive outcomes caused by increased late follicular progesterone rise.

STUDY QUESTION: Is there an association between progesterone (P4) levels on the day of hCG or GnRH trigger and on the day of oocyte retrieval in IVF/ICSI cycles? SUMMARY ANSWER: A significant positive correlation between P4 levels on the day of trigger and the day of oocyte retrieval is seen; HCG trigger induces a steeper P4 increase than GnRHa trigger. WHAT IS KNOWN ALREADY: FSH induces LH receptor (LHR) expression on granulosa cells, and LHR produces progesterone when exposed to LH-like activity. FSH per se also to some extent induces P4 secretion. Late follicular phase progesterone rise has been associated with reduced reproductive outcomes. STUDY DESIGN, SIZE, DURATION: This study is based on data from a previously published RCT conducted from 2009 to 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 384 participants were enrolled; 199 received 5000 IU hCG and 185 received buserelin 0.5 mg for triggering ovulation. P4 was measured on the day of ovulation induction and on the day of oocyte retrieval. FSH consumption and number of retrieved follicles were recorded. MAIN RESULTS AND THE ROLE OF CHANCE: A significant linear relationship between P4 on the day of ovulation induction and oocyte retrieval was seen in the hCG trigger group (P < 0.00001) as well as in the GnRHa trigger group (P < 0.00001). The P4 ratio (the increase in P4 between ovulation induction and oocyte retrieval) was significantly higher in the group of patients with <5 follicles compared to those with 5-15 and >15 follicles (P < 0.0001). The FSH consumption per follicle was significantly higher in the group of patients with <5 follicles compared to those with 5-15 and >15 follicles (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Although the study demonstrates a significant correlation between P4 levels before and after ovulation trigger, it does not demonstrate a causal relation to the number of LHRs present on granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study support the proposed hypothesis that follicles exposed to high levels of FSH during ovarian stimulation will respond with an inappropriately high LHR expression. This in turn causes a high P4 output in response to the trigger. This study further expands our understanding of the underlying mechanisms affecting reproductive outcomes in relation to ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): The authors received no specific funding for this work and disclose no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Oocyte developmental competence is improved by relatively greater circulating progesterone concentrations during preovulatory follicular growth.

This study evaluated the effect of progesterone priming during follicular growth on oocyte competence to undergo oocyte cleavage and embryo development in sheep. Two experiments were performed on a total of 195 females that either received or did not receive a progesterone treatment (CIDR-type device) during the first follicular wave, beginning soon after ovulation (i.e., Day 0 of the experiment). On Day 3, the follicular population and oocyte quality (Experiment 1 and 2) and the competence of oocytes for cleavage and embryo development (Experiment 2) were evaluated after laparoscopic ovum pickup (LOPU) and in vitro fertilization. In Experiment 1, in a 2 × 2 factorial study the progesterone priming treatment (treated or not) was or was not associated with a single dose of FSH in a slow-release hyaluronic acid preparation given on Day 0. The follicular population on Day 3 and the number and morphology of recovered cumulus oocyte complexes (COCs) were not affected by the progesterone treatment (P = NS) but were improved by the FSH administration (P <  0.05). An interaction between both treatments was observed (P <  0.05), with more desirable outcome with the females that received both the progesterone and the FSH treatments. In Experiment 2, half of the females received the exogenous progesterone priming, and all females received FSH on Day 0. After follicular aspiration on Day 3, the cleavage rate and the embryo development rate following in vitro fertilization and culture were greater in those females that received the progesterone treatment (P <  0.05). In conclusion, these studies provide evidence that progesterone treatment during follicular growth affects oocyte competence, with the greater progesterone concentrations enhancing the oocyte's capacity to undergo cleavage and embryo development.

The decline in serum estradiol on the second day after oocyte retrieval affects the outcome of IVF/ICSI-ET treatment in high ovarian responders.

OBJECTIVE: To investigate the predictive value of the decline in serum estradiol on the second day after oocyte retrieval on the outcomes of in vitro fertilization (IVF) or intra-cytoplasmic sperm injection and embryo transfer (ICSI-ET) among high ovarian responders. DESIGN: Retrospective single-center cohort study. SETTING: Tertiary-care, university-affiliated teaching hospital. Patients Women aged 20-45 years undergoing assisted reproduction treatment from June 2014 to December 2015. INTERVENTIONS: A total of 980 cycles were included; 395 high responders (Group 1) and 256 normal responders (Group 3) underwent embryo transfer (ET) in fresh ET cycles. A total of 329 high ovarian responders who underwent cryopreservation of all embryos (Group 2) were recruited as controls. The cases were divided into the following five subgroups according to the rate of serum estradiol decline on the second day after oocyte retrieval: 50.00-59.99% (Subgroup A), 60.00-69.99% (Subgroup B), 70.00-79.99% (Subgroup C), 80.00-89.99% (Subgroup D) and ≥ 90.00% (Subgroup E). The clinical outcomes were analyzed. MAIN OUTCOME MEASURES: Clinical pregnancy rate, implantation rate. RESULTS: In Group 1, the pregnancy rate decreased from 51.33 to 36.72% and the implantation rate decreased from 30.93 to 21.70% when the level of serum estradiol on the second day after oocyte retrieval decreased by more than 80%, which was a statistically significant decline (p < 0.05). The peak estradiol (E2) value and implantation rate were also significantly different (p < 0.05). In Group 2, the decline of serum E2 on the second day after oocyte retrieval had no significant effect on the clinical pregnancy rate or the implantation rate. The trend was similar in Group 3. CONCLUSIONS: A decline in the E2 level of > 80% after oocyte retrieval may play an important role in unsatisfactory IVF/ICSI-ET outcomes among high ovarian responders.