High ovarian response does not affect oocyte quality: a model based on sharing donated oocytes

Abstract Background Ovarian responsiveness to controlled ovarian stimulation is essential for a successful clinical outcome in assisted reproductive technology (ART) cycles. We aimed to find a suitable new ovulation stimulation protocol for poor ovarian response (POR) patients over 40 years old. Methods A retrospective analysis of 488 ART cycles was evaluated from January 2015 to June 2019. Comparisons were made between the flexible short protocol (FSP), routine short protocol and mild stimulation protocol. Results Compared with the routine short protocol, the FSP delayed the gonadotropin start time and reduced the total gonadotropin dose per stimulation cycle. At the same time, compared with the mild stimulation protocol, the FSP improved oocyte quality and embryo quality and improved embryo implantation potential after transfer. Furthermore, the use of the FSP reduced the probability of premature ovulation, as it inhibited the premature luteinizing hormone (LH) surge to a certain extent. Conclusions The FSP yielded better outcomes than other protocols for patients with POR over 40 years old in our study. However, further prospective studies are needed to provide more substantial evidence and to determine whether the FSP can be successful for both patients over 40 years group and younger POR patients.

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A predictive fertility treatment model based on oocyte quality and reactive oxygen species

Fertility and Sterility ◽

10.1016/j.fertnstert.2017.07.1143 ◽

2017 ◽

Vol 108 (3) ◽

pp. e318

Author(s):

R. Jeelani ◽

S.R. Aldhaheri ◽

H. Kohan-Ghadr ◽

S. Khan ◽

R.T. Morris ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oocyte Quality ◽

Fertility Treatment ◽

Oxygen Species ◽

Treatment Model ◽

Model Based

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Arginine methyltransferases mediate an epigenetic ovarian response to endometriosis

Reproduction ◽

10.1530/rep-15-0212 ◽

2015 ◽

Vol 150 (4) ◽

pp. 297-310 ◽

Cited By ~ 12

Author(s):

Claudia Baumann ◽

Mark Olson ◽

Kai Wang ◽

Asgerally Fazleabas ◽

Rabindranath De La Fuente

Keyword(s):

Transcriptional Repression ◽

Ovarian Tissue ◽

Critical Role ◽

Ovarian Response ◽

Oocyte Quality ◽

Dependent Manner ◽

Dna Hypermethylation ◽

System Disease ◽

Stage Embryo ◽

Healthy Control

Endometriosis is associated with infertility and debilitating chronic pain. Abnormal epigenetic modifications in the human endometrium have recently been implicated in the pathogenesis of this condition. However, whether an altered epigenetic landscape contributes to pathological changes in the ovary is unknown. Using an established baboon endometriosis model, early-, and late-stage epigenetic changes in the ovary were investigated. Transcript profiling of key chromatin-modifying enzymes using pathway-focused PCR arrays on ovarian tissue from healthy control animals and at 3 and 15 months of endometriosis revealed dramatic changes in gene expression in a disease duration-dependent manner. Ingenuity Pathway Analysis indicated that transcripts for chromatin-remodeling enzymes associated with reproductive system disease and cancer development were abnormally regulated, most prominently the arginine methyltransferases CARM1, PRMT2, and PRMT8. Downregulation of CARM1 protein expression was also detected in the ovary, fully-grown oocytes and eutopic endometrium following 15 months of endometriosis. Sodium bisulfite sequencing revealed DNA hypermethylation within the PRMT8 promoter, suggesting that deregulated CpG methylation may play a role in transcriptional repression of this gene. These results demonstrate that endometriosis is associated with changes of epigenetic profiles in the primate ovary and suggest that arginine methyltransferases play a prominent role in mediating the ovarian response to endometriosis. Owing to the critical role of CARM1 in nuclear receptor-mediated transcription and maintenance of pluripotency in the cleavage stage embryo, our results suggest that epigenetic alterations in the ovary may have functional consequences for oocyte quality and the etiology of infertility associated with endometriosis.

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P–198 Higher rate of direct uneven cleavage (DUC) embryos in women exhibiting high ovarian response

Human Reproduction ◽

10.1093/humrep/deab130.197 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

N Schachte. . Safrai ◽

G Karavani ◽

E Esh. Broder ◽

E Levitase ◽

T Wainstock ◽

...

Keyword(s):

Ovarian Stimulation ◽

Embryo Quality ◽

Implantation Rate ◽

Ovarian Response ◽

Oocyte Quality ◽

Similar Rate ◽

Pregnancy Rates ◽

Morphokinetic Parameters ◽

Response Group ◽

Implantation And Pregnancy Rates

Abstract Study question Does high ovarian response to controlled ovarian stimulation (COS) have a negative effect on oocyte quality? Summary answer High ovarian response is associated with reduced oocyte quality manifested as higher fraction of immature oocytes and higher rate of direct uneven cleavage (DUC) embryos. What is known already The literature regarding the effect of ovarian hyperstimulation on oocyte quality is limited and controversial. Results from several studies suggest that hyper response to controlled ovarian stimulation has a detrimental effect on oocyte and embryo quality, while others failed to confirm the existence of a direct toxic effect on oocyte and embryo quality. The association between temporal embryonal milestones and implantation rate has been previously demonstrated ,offering an additive tool by which oocyte quality, represented by embryo dynamics, can be evaluated. None of the aforementioned studies, however, used time lapse monitoring (TLM) system to evaluate oocyte and embryo quality. Study design, size, duration This study included a retrospective assessment of morphokinetic parameters performed by TLM from three university affiliated medical centers between January 2014 and December 2019. The developmental process and kinetics of 1863 embryos obtained from the study group, referred as the “ high ovarian response” (HOR) group, was compared to 4907 embryos from the control group - the “normal ovarian response” (NOR) group. Participants/materials, setting, methods The study included patients younger than 38 years who underwent COS with consecutive aspiration of either more than 15 oocytes (the HOR group) or 6–15 oocytes (the NOR group). A comparison was made between the groups regarding morphokinetic parameters, including the rate of embryos manifesting direct uneven cleavage (DUC) at first cleavage (DUC–1), as well as implantation and pregnancy rates. Logistic regression was conducted to assess the association between patients’ characteristics and implantation rate. Main results and the role of chance Oocyte maturation rate was significantly lower, and the DUC–1 embryos rate was significantly higher in the high ovarian response group compared to the normal ovarian response group (56.5% Vs 90.0%, p < 0.001 and 16.2% Vs 12.0%, p = <0.001; respectively). Following the exclusion of DUC–1 embryos, embryos from the HOR and the NOR groups reached the consecutive morphokinetic milestones at a similar rate and demonstrated similar implantation and clinical pregnancy rates. In a multivariate analysis preformed, only maternal age was found to be predictive for implantation. Limitations, reasons for caution The groups were not homogenous in their basic characteristics. Important information regarding the maximal dose of GT obtained, previous IVF response and ovarian reserve testing was lacking Wider implications of the findings: Higher oocyte quantity might have an effect on oocyte quality manifested as higher fraction of incompetent oocytes and higher rate of DUC–1 embryos. Once beyond the preliminary developmental stages, embryos from both groups reach the morphokinetic milestones at a similar rate and display similar implantation and pregnancy rates. Trial registration number Not applicable

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The two-step process of ovarian follicular growth and maturation in mammals can be compared to a fruit ripening where quality depends on the second step

Biology of Reproduction ◽

10.1093/biolre/ioab236 ◽

2021 ◽

Author(s):

Marc-André Sirard

Keyword(s):

Follicular Development ◽

Ovarian Response ◽

Oocyte Quality ◽

Second Step ◽

Stimulation Protocol ◽

Dynamic Nature ◽

Apple Ripening ◽

Ovarian Follicular Growth ◽

Biphasic Process ◽

Human Ivf

Abstract In human IVF, the main uncertainty factor impacting on success is oocyte quality, which largely depends on the follicular status at the time of collection. Decades of debate ensued to find the perfect stimulation protocol demonstrated the complexity of the ovarian response to exogenous gonadotropins and the dynamic nature of late folliculogenesis. Although several follicular markers, proteins, RNA from granulosa cells or microRNA and follicular fluid metabolites have been associated with outcome, the possibility to influence them during stimulation remains elusive. The heterogeneity of the follicle’s maturity following control ovarian stimulation is also an important factor to explain average poor oocyte quality still observed today. In this review, the analogy between the apple ripening on the tree and follicular development is presented to focus the attention on a biphasic process: growth and differentiation. The molecular analysis of the progressive follicular differentiation indicates 2 competing phenomena: growth and differentiation where a delicate balance must operate from one to the other to ensure proper maturity at ovulation. As long as FSH stimulates growth, follicles remain green, and it is only when FSH is replaced by LH that the ripening process begins, and “apples” become red. Both fruits, follicles and apples, depend on a perfect timing of events to generate offspring.

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P–614 BMI effects on oocyte quality in an egg donation program and the relationship with its first stimulation cycle

Human Reproduction ◽

10.1093/humrep/deab130.613 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

N GALIND. MATEU ◽

I Marti. Aldekoa ◽

B Amoroch. Llanos ◽

I Pére. Cano ◽

G Leó. Rodríguez ◽

...

Keyword(s):

Polycystic Ovary ◽

Ovarian Response ◽

Oocyte Quality ◽

Normal Weight ◽

Egg Donation ◽

Who Criteria ◽

Spanish Law ◽

Low Weight ◽

Registration Number ◽

Negative Effect

Abstract Study question Does body mass index (BMI) affect oocyte quality in an egg donation program and its relationship with the first stimulation cycle? Summary answer Our results indicated significant differences within BMI groups obtaining better results in donors <25 years old in quantity/quality oocyte than > 25 with normal weight. What is known already Low weight (LW) and excess weight represent a risk factor for different pathologies and may have a negative effect on the quality of the ovarian response in infertility treatments. Study design, size, duration Observational retrospective study at IVI Alicante, in which first donor cycles between 01/01/2015 and 04/30/2020 were analyzed. 307 donors were included. Groups were divided according to the BMI following the WHO criteria and were subdivided according to the protocol used (antagonists / progestogens, age, previous pregnancy and polycystic ovary syndrome (PCOS)). In all cases, the number of total, MII and immature oocytes, doses of FSH and days of stimulation were observed. Participants/materials, setting, methods Donors between 18–35 years old, in their first stimulation cycle, were distributed according to their BMI, following the WHO criteria in kg / m2 (Low weight (LW): <18, 5, Normal weight (NW): 18.5–24.9, Overweight (OW) 25–29.9 and Obese (O): ≥30). Inclusion criteria: Good state of psychophysical health and normal tests according to Spanish law on ART . Statistical analysis was performed with R statistical software, version 4.0, linear and establishing significant differences when p < 0.05. Main results and the role of chance Taking into account the general results of the BMI groups by oocytes number and MII: LW: 19.2 / 14.9; NW: 20.2 / 15.6; OW: 18.9 / 14.6, p = 0.513 / p = 0.74 respectively, we observe that with BMI groups and progestin stimulation protocols, results are reversed: No. oocytes and MII with LW: 30 / 22.5; NW: 19.2 / 14.4, OW: 20.8 / 14.8 p = 0.402 / 0.662 respectively. LW and OW are conditions which affect more in quantity than oocyte quality. Significant differences in BMI are observed when they are subdivided according to age, obtaining better results in donors <25 years of age both in quantity and oocyte quality than> 25 years: Total oocytes: LW: 22.6, NW: 21.7, OW: 20 vs LW: 14.2, NW: 17.6, SP: 16.3, p = 0.01, respectively; No. of MII oocytes LW: 17.8, NW: 16.6, OW: 14.9 vs LW: 10.5, NW: 13.9 OW: 13.8, p = 0.003, respectively. Our results reflect that the NW group is the one with better results obtained compared to the LW and OW groups both in overall number of oocytes and also in quality. The type of stimulation does not affect this group of donors. Limitations, reasons for caution More studies with clear criteria and a uniform record of results are needed. Meanwhile, the proper shortlisting should be considered if it is a BMI of NW (18.5–24.9 kg / m2) and less than 25 years. Wider implications of the findings: Analyzing other studies, there are disagreements in terms of discrimination of BMI groups and with incomplete data about of quantity, oocyte quality and oocyte stimulation, offering different results with the same parameters establishing trends in the NW group. Trial registration number Not applicable

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A predictive fertility treatment model based on oocyte quality and reactive oxygen species

Fertility and Sterility ◽

10.1016/j.fertnstert.2017.02.057 ◽

2017 ◽

Vol 107 (3) ◽

pp. e31

Author(s):

Roohi Jeelani ◽

Faten Shaeib ◽

Mili Thakur ◽

Sana Khan ◽

Husam M. Abu-Soud

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oocyte Quality ◽

Fertility Treatment ◽

Oxygen Species ◽

Treatment Model ◽

Model Based

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Effect of Continuous Administration of Enalapril Maleate on the Oocyte Quality and In Vitro Production of Parthenote Embryos in Nulliparous and Multiparous Goats Undergoing Serial Laparoscopic Ovum Pick-Up

Animals ◽

10.3390/ani9110868 ◽

2019 ◽

Vol 9 (11) ◽

pp. 868

Author(s):

Pamela A. Bravo ◽

Maria E. Moreno ◽

César C.L. Fernandes ◽

Rafael Rossetto ◽

Camila M. Cavalcanti ◽

...

Keyword(s):

Ovarian Response ◽

Oocyte Quality ◽

In Vitro Production ◽

Continuous Administration ◽

Enalapril Maleate ◽

Vitro Production ◽

To Receive ◽

Intravaginal Device

The aim of this work was to determine the effect of enalapril maleate administration, during oocyte recovery by serial laparoscopic ovum pick-up (LOPU), on the ovarian response and in vitro embryo production (IVP). Twenty cross-bred goats were allocated equally into two groups: Nulliparous and Multiparous. In each group, five animals were selected to receive daily doses of enalapril maleate during the hormonal protocol. Estrus was synchronized by a PGF2α analog, followed 48 h later by insertion of an intravaginal device with progesterone. Forty-eight hours after, a single dose of FSH/eCG was administered. The FSH/eCG doses were repeated three times, on every four day. Oocytes were recovered by LOPU 24 h after each FSH/eCG dose. Viable oocytes were matured in vitro, to be parthenogenetically activated and cultured for 72 h to the cleavage stage. The drug treatment increased the proportion of total follicles observed at LOPU (p < 0.01) in multiparous goats. In both parity groups, enalapril administration had no effect on the proportion or quality of oocytes recovered. Furthermore, the number of embryos cleaved was similar between the groups. Thus, enalapril maleate affected the ovarian response in multiparous animals only and had no effect on the oocyte quality or IVP.

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Predictors of Chances to Conceive in Ovulatory Patients during Clomiphene Citrate Induction of Ovulation in Normogonadotropic Oligoamenorrheic Infertility1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.5.5705 ◽

1999 ◽

Vol 84 (5) ◽

pp. 1617-1622

Author(s):

Babek Imani ◽

Marinus J. C. Eijkemans ◽

Egbert R. te Velde ◽

J. Dik F. Habbema ◽

Bart C. J. M. Fauser

Keyword(s):

Sperm Count ◽

Clomiphene Citrate ◽

Univariate Analysis ◽

Ovarian Response ◽

Oocyte Quality ◽

Initial Screening ◽

Younger Women ◽

Serum Lh ◽

Tubal Disease

The present prospective follow-up study was designed to identify whether clinical, endocrine, or ultrasound characteristics assessed by standardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate (CC) medication. Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease. Daily CC doses of 50 mg (increasing up to 150 mg in case of absent ovarian response) from cycle days 3–7 were used. First conception (defined as a positive urinary pregnancy test) was the end point for this study. A cumulative conception rate of 73% was reached within 9 CC-induced ovulatory cycles. Patients who did conceive presented more frequently with lower age (P < 0.0001) and amenorrhea (P < 0.05) upon initial screening. In a univariate analysis, patients with elevated initial serum LH concentrations (>7.0 IU/L) had a higher probability of conceiving (P < 0.01). In a multivariate analysis, age and cycle history (oligomenorrhea vs. amenorrhea) were identified as the only significant parameters for prediction of conception. These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea. Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients (body weight and hyperandrogenemia, as shown previously) are distinctly different from predictors of conception in ovulatory CC patients (age and the severity of cycle abnormality). This disparity suggests that the FSH threshold (magnitude of FSH required for stimulation of ongoing follicle growth and ovulation) and oocyte quality (chances for conception in ovulatory cycles) may be differentially regulated.

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Effect of aging on follicular function may be relieved by exogenous gonadotropin treatment in a sheep model

Reproduction ◽

10.1530/rep-12-0030 ◽

2012 ◽

Vol 144 (2) ◽

pp. 245-255 ◽

Cited By ~ 8

Author(s):

Fiammetta Berlinguer ◽

Antonio Gonzalez-Bulnes ◽

Antonio Spezzigu ◽

Ignacio Contreras-Solis ◽

Sara Succu ◽

...

Keyword(s):

Young Adult ◽

Age Groups ◽

Ovarian Response ◽

Oocyte Quality ◽

Developmental Competence ◽

Reproductive Aging ◽

Sheep Model ◽

Mean Values ◽

Oestrus Cycle

The current study investigated hormonal and ovarian changes during physiological reproductive aging in Sarda ewes. In a first experiment, follicular and corpus luteum dynamics were compared during an induced oestrus cycle in aged (12–14 years) and young adult ewes (4–5 years). Oestrus cycle characteristics did not differ between the two experimental groups. However, follicular function during the follicular phase showed significant alterations in aged ewes, as determined by a lack of dominance effect and by lower mean values of circulating oestradiol (E2) and inhibin levels, compared with young adult ewes. In a second experiment, differences in follicle growth, hormonal milieu and oocyte quality in response to exogenous FSH administration were assessed in aged and adult ewes. No differences were recorded in ovarian response to FSH treatment between young adult and aged ewes, as evaluated by ultrasonographic data and circulating concentrations of LH, E2 and inhibin-A. Although the total number of recovered oocytes was similar in the two age groups, the number of good quality oocytes selected for IVM was significantly lower in aged ewes compared with adult ones. Thereafter, no differences were recorded in cleavage rates, total blastocyst output, embryo developmental kinetic and quality between aged and adult groups. In conclusion, this study demonstrated that reproductive aging in sheep is associated with impaired follicle functionality and an increase in the proportion of oocytes showing morphological abnormalities. However interestingly, oocyte developmental competence in vitro and embryo cryotolerance were not affected by the aging process, when only good quality oocytes were chosen.

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