scholarly journals There is a cycle to cycle variation in ovarian response and pre-hCG serum progesterone level: an analysis of 244 consecutive IVF cycles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sule Yildiz ◽  
Kayhan Yakin ◽  
Baris Ata ◽  
Ozgur Oktem

Abstract We aimed to answer one key question, that was not previously addressed as to whether serum progesterone (P4-hCG day) and its co-variates (estradiol (E2-hCG day) and the number of retrieved oocytes) of a given cycle can be predictive of the subsequent cycle when both cycles are consecutive and comparable for the stimulation protocol, gonadotropin dose and duration of stimulation. We analyzed such 244 consecutive (< 6 months) IVF cycles in 122 patients with GnRH agonist long protocol and found that P4, E2 and the number of retrieved oocytes significantly vary between the two cycles. Although P4 increased (ranging from 4.7 to 266.7%) in the 2nd cycle in 61 patients, E2 and the number of retrieved oocytes, which are normally positively correlated with P4 paradoxically decreased in the 41% and 37.7% respectively, of these same 61 patients. When a similar analysis was done in the 54 out of 122 patients (44.3%) in whom serum P4 was decreased in the 2nd cycle, the mean decrease in P4 was − 34.1 ± 23.3% ranging from − 5.26 to − 90.1%. E2 and the number of retrieved oocytes paradoxically increased in the 42.3% and 40.7% of these 54 patients respectively. P4 remained the same only in the 7 (5.7%) of these 122 patients. These findings indicate that late follicular phase serum P4 may change unpredictably in the subsequent IVF cycle. The changes are not always necessarily proportional with ovarian response of previous cycle suggesting that growth characteristics and steroidogenic activities of antral cohorts may exhibit considerable cycle to cycle variations.

1976 ◽  
Vol 83 (4) ◽  
pp. 684-691 ◽  
Author(s):  
Sven Johan Nillius ◽  
Leif Wide

ABSTRACT Modulating effects of oestradiol-17β and progesterone on the pituitary responsiveness to luteinizing hormone-releasing hormone (LRH) were investigated in 12 women with functional amenorrhoea. The pituitary reserve capacity for gonadotrophin section was investigated with repeated intravenous LRH tests before and after administration of oestradiol-1β followed by either progesterone or saline. Intramuscular injection of 1 mg of oestradiol-17β benzoate resulted in a suppression of both the basal gonadotrophin levels in serum and the gonadotrophin responses to LRH 24 h later. Progesterone, 25 mg im, was then administered in eleven experiments. Six h later, when the mean serum progesterone level had increased to levels similar to those seen in the early post-ovulatory phase of the menstrual cycle, there was a marked augmentation of the pituitary capacity to release both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to LRH. This was not found in eight experiments where saline was given instead of progesterone after oestrogen pretreatment. These findings suggest that the greatly increased pituitary sensitivity to LRH at midcycle may be caused not only by the oestradiol increase in blood during the late follicular phase but also in part by the small pre-ovulatory rise of progesterone during the mid-cyclic LH peak. Furthermore, they add further support to the hypothesis that progesterone as well as oestradiol is involved in the induction of the LH peak at midcycle. Progesterone may be of importance to secure the release of enough LH for ovulation and normal corpus luteum formation to occur.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A R Neves ◽  
S Santos-Ribeiro ◽  
S Garcí. Martínez ◽  
S Soares ◽  
J A García-Velasco ◽  
...  

Abstract Study question Is late-follicular phase progesterone elevation (PE) associated with a deleterious effect on embryo euploidy, embryo blastulation and cumulative live birth rates (CLBRs)? Summary answer Late-follicular phase PE has no impact on impact on embryo euploidy rate, embryo blastulation rate nor on the CLBR. What is known already The effect of PE in ART outcomes has been extensively studied, yielding so far conflicting results. While some authors claim it is only detrimental to endometrial receptivity, others have suggested that it may also impair oocyte/embryo quality. Moreover, little is known regarding the potential effect PE may have on embryo ploidy and, consequently, CLBR. Study design, size, duration A multicenter retrospective cross-sectional study was performed between August 2017 and December 2019. A total of 1495 ICSI cycles coupled with preimplantation genetic diagnosis for aneuploidies (PGT-A) and deferred frozen embryo transfer (FET) were analyzed. Participants/materials, setting, methods All patients underwent ovarian stimulation with GnRH antagonist protocol and performed a serum progesterone measurement at one of the participating private fertility clinics on the day of trigger. The sample was stratified according to the progesterone levels: normal (≤1.50 ng/ml) and high (&gt;1.50 ng/ml). The primary outcome was the embryo euploidy rate. Secondary outcomes were the number of euploid blastocysts, the blastulation rate and CLBR. Main results and the role of chance Late-follicular phase PE was associated with higher late-follicular estradiol levels (2847.56±1091.10 pg/ml vs. 2240.94± 996.37 pg/ml, p &lt; 0.001) and more oocytes retrieved (17.67±8.86 vs. 12.70±7.00, p &lt; 0.001). The number of euploid embryos was higher in the PE group (2.32±1.74 vs. 1.86±1.42, p &lt; 0.001), whereas the embryo euploidy rate (48.3% [44.9%–51.7%] vs. 49.1% [47.7%–50.6%] and blastulation rate (47.1% [43.7%–50.5%] vs. 51.0% [49.7%–52.4%]) were comparable between the two groups. Likewise, no significant differences were found regarding the live birth rate (LBR) after the first FET (34.1% vs. 31.1%, p = 0.427) nor the CLBRs (38.9% vs. 37.0%, p = 0.637). Mixed-model analysis was performed in order to account for the clustering of cycles in the same patient. Adjusting for patients’ age, PE and BMI, PE failed to demonstrate any effect on the embryo euploidy rate (OR 1.03 [95% CI 0.89–1.20]). Mixed-model analysis for the number of euploid embryos was also performed. After adjusting for PE, age, BMI and ovarian response, PE did not affect the number of euploid embryos (0.02 [95%CI –0.21;0.25]. Multivariate logistic regression adjusted for PE, age, BMI and ovarian response revealed that PE was not associated with the CLBR (adjOR 0.96 [95% CI 0.66–1.38]). Limitations, reasons for caution Limitations of the study include its retrospective nature. Moreover, including only GnRH antagonist protocol and ICSI does not allow the extrapolation of these results to other populations. Wider implications of the findings: Our findings question results from previous studies claiming a detrimental effect of PE on embryo implantation potential. According to our results, PE has no impact on embryo euploidy rate, blastulation rate nor on CLBRs. Trial registration number Not applicable


2019 ◽  
Vol 104 (11) ◽  
pp. 5555-5565 ◽  
Author(s):  
Jingjie Li ◽  
Yue Gao ◽  
Lihuan Guan ◽  
Huizhen Zhang ◽  
Pan Chen ◽  
...  

Abstract Context Late follicular phase elevation in serum progesterone (P) during controlled ovarian hyperstimulation negatively affects the outcome of assisted reproductive technology by contributing to endometrial-embryo asynchrony. There are still no data on lipid metabolite alterations during this process. Objectives To investigate alterations in the lipid profile during the window of implantation in patients with premature P rise. Design Lipidomic variations in the endometrium were evaluated by ultrahigh-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry. Setting University assisted reproductive medicine unit. Patients or Other Participants Forty-three patients undergoing in vitro fertilization/intracytoplasmic sperm injection because of a tubal factor or male factor infertility were included in this study. The patients were divided into a high P group (P ≥ 1.5 ng/mL, 15 patients) and a normal P group (P < 1.5 ng/mL, 28 patients) on the day of human chorionic gonadotropin administration. Interventions The endometrial tissues were obtained by Pipelle biopsy 7 days after human chorionic gonadotropin administration. Main Outcome Measures Alterations in lipid metabolites. Results A total of 1026 ions were identified, and 25 lipids were significantly upregulated. The endometrial lipid profile was characterized by substantial increases in the concentrations of phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, diacylglycerol, ceramide, phosphatidylinositol, and phosphatidylserine in patients with a premature P rise at the end of the follicular phase. The correlation analysis between P levels and lipids showed a stronger negative correlation between phosphatidylethanolamine or phosphatidylserine and P levels. Conclusions Premature P elevation disrupts the lipid homeostasis of the endometrium during the peri-implantation period. The altered lipid levels may impair endometrial receptivity and early embryo implantation.


2014 ◽  
Vol 29 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Charlotte Sonigo ◽  
Géraldine Dray ◽  
Clémence Roche ◽  
Isabelle Cédrin-Durnerin ◽  
Jean-Noel Hugues

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Ab. ali ◽  
B Lawrenz ◽  
A L Tegedor ◽  
F R Ruiz ◽  
A El-Damen ◽  
...  

Abstract Study question Does the ratio of serum progesterone (P4) to the number of follicles (P4/Follicle) on the day of final oocyte maturation affect the ploidy status of the embryos? Summary answer A high P4/Follicle ratio negatively affects the euploid rate of the embryos. What is known already During ovarian stimulation, exogenous gonadotropins are administered to achieve multifollicular growth. Intense gonadotropin stimulation towards the end of the follicular phase seems to cause a premature progesterone rise in stimulated IVF cycles. The impact of serum progesterone elevation during the follicular phase has been studied intensively. Though most studies have focused on the effect of progesterone elevation on the endometrial receptivity, little is known about its possible impact on embryo development and ploidy status. The only study that investigated the effect of progesterone on the embryo ploidy status, was unable to show any significant impact. Study design, size, duration This retrospective study was performed at ART Fertility Clinics Abu Dhabi, UAE and Muscat, Oman. All stimulation cycles (n = 975) were performed between January 2015 to December 2019 with patients aged between 18–45, Body mass index (BMI) of 18–35, stimulated either with rFSH or hMG. All embryos underwent ICSI and Preimplantation Genetic Testing for Aneuploidies (PGT-A),Patients with surgical sperm extraction, warmed oocytes or natural cycle IVF were excluded. Participants/materials, setting, methods Serum P4 was measured on the last ultrasound prior triggering for final oocyte maturation. The P4/Follicle ratio was calculated as the ratio of P4 on trigger day to the number of follicles &gt; 10 mm on the last ultrasound. Serum P4 and P4/Follicle ratio were then analyzed using linear and univariate regression model to find potential correlation with the number of oocytes retrieved, number of mature oocytes, embryo quality (day 3 and 5), and euploid rate. Main results and the role of chance A total of 975 cycles were analyzed, with a mean age of 33.88±0.05 years, a mean BMI of 26.7±0.035 kg/m2. The mean number of oocytes collected was 12.53±0.058. Mean serum P4 on trigger day was 0.83±0.005 ng/ml and higher serum P4 values were observed as the number of oocytes retrieved and the number of mature oocytes increased (β = 0.026, p &lt; 0.0001 and β = 0.028, p &lt; 0.001, respectively). On the other hand, the mean P4/Follicle ratio was 0.056±0.00041 ng/ml and, unlike serum P4, the P4/Follicle ratio showed a negative correlation with the number of oocytes retrieved as well as with the number of mature oocytes (β=–0.001, p &lt; 0.001 and β=–0.001, p &lt; 0.001, respectively). While day 3 embryos were not affected by serum P4 or P4/Follicle ratio, the blastocyst quality was negatively affected by both increasing serum P4 levels and the P4/Follicle ratio (β=–0.012 p &lt; 0.05, β=–0.002, p &lt; 0.001, respectively). Euploid rates were positively correlated in cycles with increased serum P4 β = 0.18, p &lt; 0.001), while negatively correlated in cycles with a high P4/Follicle ratio (β=–0.015, p &lt; 0.001). After adjusting for potential confounders, only P4/Follicle remained as a significant negative factor for euploid rate (β=–0.004, p &lt; 0.001, 95% CI: –0.007- –0.001, p &lt; 0.001), which was not observed for serum P4 (p = 0.46). Limitations, reasons for caution This is an observational study based on retrospective data; an improved extrapolation of the results might be obtained by performing a prospective study. Wider implications of the findings: The findings of this study should encourage clinicians to optimize the ovarian stimulation protocols not only based on serum P4, but also considering the P4/Follicle ratio. Trial registration number Not applicable


1998 ◽  
Vol 156 (1) ◽  
pp. 91-98 ◽  
Author(s):  
L Riboni ◽  
C Escamilla ◽  
R Chavira ◽  
R Dominguez

The effects of peripheral sympathetic denervation induced by guanethidine administration to newborn and 10-day-old female guinea pigs on puberty, ovulation and the follicular population were analysed. Peripheral sympathetic denervation beginning at birth resulted in the loss of ovarian norepinephrine content (0.95. +/- 0.1 ng/mg wet tissue in untreated control animals vs non detectable in treated animals). Guanethidine administration to newborn or 10-day-old guinea pigs advanced puberty (age of vaginal opening: 27 +/- 1.2 days (newborn), 26 +/- 1.7 (10-day-old) vs 37 +/- 0.7 (control), P < 0.001) and ovulation. The number of corpora lutea in control and denervated animals was similar (3.5 +/- 0.2 vs 3.3 +/- 0.3). The relative weight (mg/100 g body weight) of the ovaries and adrenals in the denervated animals autopsied during the late follicular phase (24-48 h after vaginal opening) increased (ovaries: 27.8 +/- 1.3, 28.9 +/- 3.0 vs 20.9 +/- 0.8, P < 0.05; adrenals 36.4 +/- 1.4, 37.0 +/- 0.8 vs 31.6 +/- 1.5, P < 0.05), while the uterine weight diminished (179 +/- 13, 149 +/- 28 vs 292 +/- 20). When the animals were killed during the late luteal phase (9-11 days after vaginal closure), the relative weight of the ovaries of newborn guanethidine-treated animals was higher than that of the control animals (21.4 +/- 1.7 vs 16.8 +/- 1.4, P < 0.05). The mean number of follicles counted in the ovaries of denervated animals was significantly higher than in control animals (1736 +/- 230 vs 969 +/- 147, P < 0.05). The mean diameter of the follicles in the untouched control ovary in animals killed in the late follicular phase was significantly larger than from animals killed in the late luteal phase (263 +/- 3.9 microns vs 248 +/- 3.0 microns, P < 0.01). The mean diameter of the follicles measured in the ovaries of denervated animals was significantly higher than in controls (animals treated from birth 274 +/- 2.0 microns vs 255 +/- 2.4, P < 0.05; animals treated from day 10, 286 +/- 2.3 microns vs 257 +/- 2.3, P < 0.05). When the mean diameter of the follicles in the left and right ovary of the untouched control was analysed, the follicular diameter in the left ovary was significantly larger than in the right ovary (309 +/- 6.0 microns vs 214 +/- 3.9, P < 0.01); the response of the left and right ovaries to sympathetic denervation was the opposite. The results obtained in the present study suggest that ovarian innervation plays a role in the regulation of follicular growth, maturation and atresia which is not related to changes in steroid secretion by the ovary, but to other regulatory mechanisms.


1964 ◽  
Vol 6 (2) ◽  
pp. 189-194 ◽  
Author(s):  
R. H. F. Hunter

1. The effects of gonadotrophins administered during the follicular phase of the oestrous cycle were studied in forty gilts; these were purebred Large White or Large White crosses weighing from 200-275 lb.2. Superovulation was induced by a subcutaneous injection of PMS; half of the animals received in addition an intramuscular injection of LH.3. All animals which received gonadotrophins exhibited normal oestrous behaviour and only four of the gilts failed to come into oestrus by Day 21 of the cycle.4. A relationship has been established between the PMS dose and the mean ovarian response.5. An injection of LH was not essential for ovulation after treatment with PMS. Similarly, it had no significant effect on ovarian response.6. Egg recovery was 75% in the group of animals that exhibited fertility. Of these eggs, 93% were fertilised and undergoing cleavage.


2005 ◽  
Vol 152 (3) ◽  
pp. 411-418 ◽  
Author(s):  
Riikka Leminen ◽  
Taneli Raivio ◽  
Sirpa Ranta ◽  
Joachim Oehler ◽  
Helena von Hertzen ◽  
...  

Objective: Low dose mifepristone (RU486) is highly effective in emergency post-coital contraception (EC), although the mechanism(s) of action remains unclear. We studied the endocrine actions of 10 mg mifepristone administered orally as a single dose to eight healthy volunteers (aged 20–45 years) during the late follicular phase. Methods: Serum levels of LH, FSH, oestradiol, progesterone, leptin, mifepristone, cortisol, and gluco-corticoid bioactivity (GBA) were measured before and 1, 2, 4 and 8 h after ingestion of mifepristone on cycle day 10 or 11 (study day 1), and follow-up was continued for 10 days. Ovarian ultrasonography was performed on study days 1 and 7. Similar measurements were carried out during a control cycle. Results: Mifepristone postponed ovulation, as evidenced by a 3.4±1.1 day (means±s.d.) delay (P < 0.005) in the LH surge and 3.6±4.0 day prolongation of the treatment cycle (P = 0.08). During the mifepristone cycle, an LH surge was displayed by five subjects when serum mifepristone levels had declined to 9.5±7.1 nmol/l. During the day of mifepristone administration, circulating GBA (P < 0.001) and leptin (P < 0.001) levels declined. On the day after mifepristone administration, mean serum FSH and leptin levels were lower than pretreatment values (3.8±1.8 IU/l vs 5.2±1.1 IU/l, n = 7, P < 0.05; 28.9±6.7 μg/l vs 33.2±9.0 μg/l, n = 7, P < 0.05 respectively), and the corresponding difference in the mean serum oestradiol concentration was borderline (452±252 pmol/l vs 647±406 pmol/l, n = 7, P = 0.056). In contrast to the control cycle, individual leptin levels declined during the follow-up after ingestion of mifepristone (n = 8, P < 0.01). Conclusions: These data showed that the commonly employed dose of mifepristone for EC delays ovulation and prolongs the menstrual cycle, when given during the late follicular phase. The mechanism of action of mifepristone may include a reduction of FSH secretion via a decrease in circulating leptin.


2021 ◽  
Author(s):  
Ting Yu ◽  
Di Wu ◽  
Jun Zhai

Abstract Background: The optimum number of oocytes retrieved by the follicular phase long-acting long protocol is still unknown. This study aimed to analyze the optimum oocyte number in patients with polycystic ovary syndrome (PCOS) undergoing this protocol.Methods: A total of 1816 PCOS patients aged <35 years who were undergoing their first cycle of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) between January 2017 and June 2019 were identified and reviewed. All patients underwent stimulation using a follicular phase long-acting long protocol. In this retrospective cohort study, patients were categorized into seven groups according to the number of oocytes retrieved (group A, 1–5; group B, 6–10; group C, 11–15; group D, 16–20; group E, 21–25; group F, 26–30; group G, >30). The main outcome indicators were the rates of high-quality embryo, fresh cycle pregnancy, cumulative pregnancy, and “freezing all” for high ovarian response. The cumulative pregnancy and “freezing all” rates for high ovarian response were analyzed using multivariate logistic analysis.Results: The high-quality embryo rate decreased with the increase in the number of oocytes retrieved (P<0.001). In the <20 oocyte group, the clinical and cumulative pregnancy rates increased with the number of oocytes retrieved, and the “freezing all” rate for high response was within 30%. In the >20 oocyte group, with an increase in the number of oocytes retrieved, no significant change was found in the clinical and cumulative pregnancy rates (P>0.05); however, the incidence of “freezing all” rate for high response was significantly increased (P<0.001). After correcting for confounding factors, the number of oocytes retrieved was an independent predictor of the “freezing all” rate for high ovarian response (odds ratio [OR], 1.085; 95% confidence interval [CI] 1.057–1.113) and cumulative pregnancy rate (OR 1.091, 95% CI 1.057–1.126). The high-quality embryo rate was significantly affected by the cumulative pregnancy rate (OR, 59.076; 95% CI: 29.591–117.938).Conclusion: In PCOS patients aged <35 years treated using the follicular phase long-acting long protocol, considering clinical outcomes, laboratory indicators, and safety, appropriate ovarian stimulation should be used to control the number of oocytes retrieved at 11–20.


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