Outcomes of BRCA pre-implantation genetic testing according to the parental mutation origin: a cohort study.

BACKGROUND: The process of gamete formation and early embryonic development involves rapid DNA replication, chromosome segregation and cell division. These processes may be affected by mutations in the BRCA1/2 genes. The aim of this study was to evaluate BRCA mutation inheritance and its effect on early embryonic development according to the parental origin of the mutation. The study question was approached by analyzing in vitro fertilization cycles (IVF) that included pre-implantation testing (PGT-M) for a BRCA gene mutation. METHODS: This retrospective cohort study compared cycles of pre-implantation genetic testing for mutations (PGT-M) between male and female patients diagnosed with BRCA 1/2 mutations (cases), to a control group of two other mutations with dominant inheritance (myotonic dystrophy (MD) and polycystic kidney disease (PKD)). Results were compared according to mutation type and through a generalized linear model analysis. RESULTS: The cohort included 88 PGT-M cycles (47 BRCA and 41 non-BRCA) among 50 patients. Maternal and paternal ages at oocyte retrieval were comparable between groups. When tested per cycle, FSH dose, maximum estradiol level, oocytes retrieved, number of zygotes, and number of embryos available for biopsy and affected embryos, were not significantly different among mutation types. All together 444 embryos were biopsied: the rate of affected embryos was comparable between groups. Among BRCA patients, the proportion of affected embryos was similar between maternal and paternal mutation origin (p = 0.24). In a generalized linear model analysis, the relative oocyte yield in maternal BRCA patients was significantly lower (0.7, as related to the non BRCA group)(p < 0.001). Zygote formation and blastulation were not affected by the BRCA gene among paternal cases (P = 0.176 and P = 0.293 respectively), nor by paternal versus maternal BRCA carriage (P = 0.904 and P = 0.149, respectively). CONCLUSIONS: BRCA PGT-M cycles performed similarly compared to non-BRCA cycles. Inheritance rate and cycle parameters were not affected by the parental origin of the mutation.

Does contemporary ART lead to pre-eclampsia? A cohort study and meta-analysis.

PURPOSE: Recent publications suggested that the risk for pre-eclampsia (PE) is higher with frozen-thawed embryo transfers (FETs) compared to fresh transfers (IVF-ETs). These studies were based on old data that reflects outdated practices. In this paper, we wanted to assess the incidence of PE in current assisted reproductive technology (ART) practice. METHODS: In this cohort study, we present the incidence of PE in all births in the province of Ontario, Canada, for the years 2013-2017 for FET, IVF-ET, and natural conceptions (NC). We also compare our findings to previous studies in a meta-analysis that includes over 4 million births. RESULTS: The results of our study show that contemporary practice of ART results in comparable risk for PE between FET and IVF-ET; however, the risk is higher than NC. CONCLUSION: Current ART practice is associated with a lower risk for PE in frozen embryo transfer; this RR can be further attenuated by using ovulatory endometrial preparation for FETs.

Oral contraceptive pills as an option for non-surgical management of retained products of conception - a preliminary study.

Many Patients with persistent retained products of conception prefers to avoid surgical interventions, such as a dilatation and curettage (D&C) that might pose an additional future risk to their already compromised fertility or obstetric performance. The aim of this study was to the possibility of induced withdrawal bleeding following oral contraceptive administration as a non-surgical treatment for patients with persistent retained products of conception (RPOC). A retrospective study of patients presenting with retained products of conception (RPOC) after failed expectant management or after treatment with PGE1 was performed. Twelve women presenting with RPOC at ≤8 weeks gestation with minimal to mild vaginal bleeding and no signs of infection were treated with oral contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%) successfully expelled the RPOC after completing the three-week course of OCPs. The three cases (25%) that did not resolve following OCP treatment had pregnancy products with positive blood flow on Doppler examination. We conclude that OCPs may be a useful medical treatment option for persisting RPOC in selected patients with absence blood flow on Doppler examination wishing to avoid surgical intervention.

Intramuscular versus Vaginal Progesterone Administration in Medicated Frozen Embryo Transfer Cycles: A Randomized Clinical Trial Assessing Sub-Endometrial Contractions.

OBJECTIVE: The study aimed to assess whether sub-endometrial contractility is reduced by the use of intramuscular (IM) progesterone. DESIGN: This is a randomized clinical trial. Patients assigned to a medicated day 5 frozen embryo transfer (FET) were randomly allocated to "vaginal progesterone" or "IM progesterone": patients randomized to the vaginal arm were treated with 200 mg micronized progesterone 3 times daily while patients randomized into the IM progesterone arm were treated with a single daily injection of 50 mg progesterone in oil. The main outcome measure was the number of sub-endometrial contractions (waves) per minute 1 day before a blastocyst embryo transfer. RESULTS: Thirty-four patients were enrolled. The progesterone serum concentration was significantly higher in patients using the IM progesterone (85.2 ± 50.1 vs. 30.3 ± 11.2 nmol/L, respectively) but this did not translate into a lower sub-endometrial contractility (2.4 ± 4.8 vs. 1.4 ± 1.1 contraction/min, respectively). Clinical pregnancy rates were comparable between groups. The number of sub-endometrial waves was significantly lower among pregnant patients (p = 0.02). CONCLUSIONS: The use of IM progesterone in medicated FET cycles does not reduce the sub-endometrial activity compared to vaginal progesterone administration. Our data support a poor clinical pregnancy outcome with high wave activity, regardless of the progesterone mode.

What maintains the high intra-follicular estradiol concentration in pre-ovulatory follicles?

PURPOSE: The purpose of the study was to establish the mechanism by which the estrogen concentration difference between the follicular fluid and the serum is maintained. METHODS: We used dialysis membrane with a pore size of <3 KD to characterize the estrogen-binding capacity of the follicular fluid. We performed PCR, western blot, and ELISA on luteinized granulosa cells to determine if sex hormone-binding globulin (SHBG) is produced by granulosa cells, and finally we used affinity columns and mass spectrometry to identify the estrogen-binding protein in the follicular fluid. RESULTS: We found that a significant estrogen concentration difference is maintained in a cell-free system and is lost with proteolysis of the follicular fluid proteins. Luteinized granulosa cells are likely not a source of SHBG, as we were not able to detect expression of SHBG in these cells. Perlecan was the most highly enriched follicular fluid protein in the affinity columns. CONCLUSIONS: We were able to identify perlecan as the most likely candidate for the major estrogen-binding protein in the follicular fluid.

Clinical pregnancy rate following frozen embryo transfer is higher with blastocysts vitrified on day 5 than on day 6.

PURPOSE: The aim of this study was to compare the pregnancy rates between good quality blastocysts vitrified on day 6 versus blastocysts vitrified on day 5 after fertilization. METHODS: This is a retrospective cohort study of 791 freeze-thaw cycles of blastocysts vitrified either on day 5 or on day 6 and transferred between January 2012 and October 2015. Five hundred and thirty-seven cycles included blastocysts vitrified on day 5, and 254 cycles included blastocysts vitrified on day 6. RESULTS: The age of the patients and the proportion of embryos that survived the thawing process were comparable between the two groups. More good quality embryos were transferred in the group in which blastocysts were vitrified on day 6 (1.2 vs. 1.3, p = 0.005), but the clinical pregnancy rate (44 vs. 33 %, p = 0.002) and the ongoing pregnancy rate (41 vs. 28 %, p < 0.001) were higher in the group in which blastocysts were vitrified on day 5. Multivariate regression analysis adjusting for patient's age, number of good quality embryos transferred (≥3BB), and treatment protocol demonstrated that the day 6 vitrified group had a significantly lower clinical pregnancy rate compared to the day 5 vitrified group (OR 0.54, 95 % CI 0.38-0.76). CONCLUSIONS: The clinical pregnancy rate following frozen embryo transfer is significantly lower with blastocysts vitrified on day 6 compared to blastocysts vitrified on day 5.

Non-synchronized endometrium and its correction in non-ovulatory cryopreserved embryo transfer cycles.

The aim of this case series study was to investigate the effect of adjusting the length of progesterone exposure on clinical pregnancy rates in cryopreserved embryo transfer cycles of patients with out-of-phase classic endometrial dating. Eighty infertile women with previous implantation failure and good-quality embryos underwent endometrial biopsy before cryopreserved embryo transfer and were included in this study. The main outcome measures were clinical pregnancy rate and histologic endometrial dating. After adjusting the length of progesterone exposure according to endometrial dating, a significantly higher implantation rate was observed in blastocyst transfers (P = 0.02) and the clinical pregnancy rate for all cycles was 36.4%, similar to that in patients with in-phase endometrium (22.5%). In conclusion, the use of classic histologic endometrial dating to estimate the timing of the window of implantation and to adjust progesterone exposure accordingly may increase the implantation rate in frozen embryo transfer cycles.

A pilot study to evaluate a device for the intravaginal culture of embryos.

The aim of this comparative randomized embryology trial was to determine if an intravaginal culture device (IVC) can provide acceptable embryo development compared with conventional IVF. Ten women between the ages of 27 and 37 years with an indication for IVF treatment were included in this study. After ovarian stimulation, oocytes were randomized to fertilization in the IVC device or using conventional IVF. Fertilization rates were higher in the IVF group compared with the IVC device (68.7% ± 36 % versus 40.7% ± 27%), respectively, whereas cleavage rates were similar (93% ± 1.5% versus 97% ± 6%) for both groups. A significantly lower number of embryos of suitable quality for transfer was obtained from the IVC device compared with conventional IVF (OR, 0.47; 95% CI, 0.26 to 0.87). The clinical pregnancy rate from transfer of IVC device embryos was 30%. Satisfaction questionnaires were also completed by all participants. Most women (70%) placed high importance on having had fertilization and embryo development occur while carrying the device. Overall, the IVC device produced reasonable pregnancy rates suggesting this technology may have a place under certain circumstances. Cost-benefit analysis, psychological factors and future studies must be considered.

A novel compound heterozygous mutation of the luteinizing hormone receptor -implications for fertility.

The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) belongs to the family of G-protein coupled receptors and binds both luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Ligand-receptor interaction mediates a downstream cascade of events which is essential for ovulation in women, and expression of the male phenotype in men. The human LHCGR gene consists of 11exons and 10 introns. Homozygous and compound heterozygous mutations may inactivate the receptor by altering its structure and subsequent function. Herein we reported a novel, compound heterozgygous inactivating LHCGR mutation in a woman who presented with secondary infertility, having previously carried to term a donor oocyte pregnancy. A 27 bp deletion was detected in exon I at amino acid number 12. This mutation involved the signal peptide region, which is important for protein targeting, maturation and cellular expression. Another mutation involving a 2 base pair (thymine and cytosine) deletion was detected in exon 11 at amino acid number 586. This deletion produced a frameshift resulting in a premature stop codon and a truncated protein. An XY sibling with the same mutations was phenotypically female and misdiagnosed as complete androgen insensitivity syndrome. Other unaffected family members were genetically tested and carried one of the two mutations.

Long-term Risk for Type 1 Diabetes and Obesity in Early Term Born Offspring: A Systematic Review and Meta-Analysis.

CONTEXT: Prematurity increases the long-term risks for endocrine and metabolic morbidity of offspring, but there is uncertainty regarding the risks for early-term deliveries (370/7-386/7 weeks of gestation). OBJECTIVE: We aim to evaluate whether early-term deliveries increase the long-term risk for type 1 diabetes and obesity of offspring up to the age of 18 years compared with full-term children. PubMed, Medline, and EMBASE were searched. Observational cohort studies addressing the association between early-term delivery and long-term risk for type 1 diabetes and obesity, were included. Two independent reviewers extracted data and assessed risk of bias. Pooled relative risks (RRs) and heterogeneity were determined. Publication bias was assessed by funnel plots with Egger's regression line and contours, and sensitivity analyses were performed. RESULTS: Eleven studies were included following a screen of 7500 abstracts. All studies were scored as high quality according to the Newcastle-Ottawa Quality Assessment Scale. Early-term delivery was significantly associated with an increased risk for type 1 diabetes (RR 1.19, 1.13-1.25), while the association was weaker for overweight and obesity (RR 1.05, 0.97-1.12). It is challenging to determine whether the association between early-term births and long-term morbidity represents a cause and effect relationship or is attributable to confounders. Most of the included studies adjusted for at least some possible confounders. CONCLUSION: Compared with full-term offspring, early-term delivery poses a modest risk for long-term pediatric type 1 diabetes. Our analysis supports that, whenever medically possible, elective delivery should be avoided before 39 completed weeks of gestation.

Can cycle day 7 FSH concentration during controlled ovarian stimulation be used to guide FSH dosing for in vitro fertilization?

BACKGROUND: When stimulating a patient with poor ovarian response for IVF, the maximal dose of gonadotropins injected is often determined by arbitrary standards rather than a measured response. The purpose of this study was to determine if serum FSH concentration during an IVF stimulation cycle reflects follicular utilization of FSH and whether serum FSH values may inform dose adjustments of exogenous FSH. METHODS: In this retrospective cross sectional study we studied 155 consecutive IVF cycles stimulated only with recombinant human FSH. We only included long GnRH agonist protocols in which endogenous FSH levels were suppressed. We correlated the serum concentration of cycle day (CD) 7 FSH with the number of oocytes retrieved, cleaving embryos and pregnancy rate. RESULTS: We found that a CD7 FSH concentration above 22 IU/L was associated with poor response regardless of the daily dose of FSH injected and a lower pregnancy rate. CONCLUSIONS: We concluded that CD7 FSH concentration during stimulation could be used to guide FSH dosing in poor responders. If the CD7 FSH concentration is above 22 IU/L increasing the dose of FSH in an attempt to recruit more growing follicles is unlikely to be successful.

Boosting Dose of Pfizer-BioNtech mRNA Vaccine Against SARS-CoV-2 Does Not Affect Reproductive Outcomes in In-Vitro Fertilization Patients: A Cohort Study.

Background: Since the introduction of anti-COVID-19 mRNA vaccination, few studies have shown that reproductive outcomes in artificial reproductive technology (ART) treatments are not impaired, after receiving the two-dose regimen. Our aim was to investigate whether a boosting dose of the Pfizer-BioNtech mRNA vaccine affects reproductive outcomes in ART patients. Materials and Methods: This is a prospective observational study, including 157 consecutive in-vitro fertilization (IVF) cycles between October 1, 2021, and November 24, 2021, in a single university affiliated IVF unit. We included female patients going through an ART procedure and male partners in cases of utilization of a fresh sperm sample. The study population was divided into four groups according to exposure status: vaccinated and boosted patients (three total doses of Pfizer-BioNtech mRNA vaccine), patients who were vaccinated without the booster dose (one or two vaccine doses), PCR-confirmed convalescent COVID-19 patients, and unvaccinated nonconvalescent patients. Main outcome measure was clinical pregnancy rate. Results: In total, 99 (63%) female patients were vaccinated three times, 24 (15.3%) were vaccinated without the booster dose, 21 (13.4%) were convalescent, and 13 were (8.3%) unexposed. Although age differed between study groups, vaccination exposure status did not affect treatment outcome: clinical pregnancy rates, maximal estradiol levels, and number of oocytes retrieved did not differ significantly between study groups (p = 0.78, 0.50, and 0.97, respectively). Vaccinated patients who received a boosting vaccine dose were treated within 43.3 ± 30.9 days after receiving the last dose, whereas vaccinated, nonboosted, or convalescent patients were treated 168.7 ± 53 and 209.6 ± 85.1 days after their last exposure, respectively. We stratified the male cohort according to boosting vaccine dose status. Sperm concentration and motility did not differ significantly after boosting (p = 0.49 and 0.49, respectively). Conclusions: Our results provide further reassurance that IVF outcomes are not affected by the anti-SARS-CoV-2 Pfizer-BioNtech mRNA vaccine, in particular the three-dose regimen.

Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF.

BACKGROUND: To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. METHODS: A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. RESULTS: A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. CONCLUSION: Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women.

Luteal phase support in fresh and frozen embryo transfers.

Context: Luteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome. Search strategy: A search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented. Conclusions: We present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment.

Mild COVID-19 Was Not Associated with Impaired IVF Outcomes or Early Pregnancy Loss in IVF Patients.

Data collection regarding the effects of COVID-19 on reproduction is ongoing. This study examined the effect of COVID-19 on IVF cycle parameters and early pregnancy outcomes. It included two arms: the first compared non-exposed cycles to post-SARS-CoV-2 IVF cycles. Sperm parameters were also compared. The second, prospective arm compared pregnancy outcomes among IVF patients who contracted COVID-19 during early pregnancy to those who did not. None of the patients were vaccinated against SARS-CoV-2. The first arm included 60 treatment cycles of women with confirmed COVID-19, compared to 60 non-exposed cycles (either the same patient before exposure or matched non-exposed patients). The outcomes of the treatment cycles did not differ significantly between exposed and non-exposed groups, including number of oocytes, endometrial thickness, fertilization rate and number of top-quality embryos. In 11 cycles, the male partner had also recently recovered: sperm concentration was lower post-exposure: 6.27 million/mL vs. 16.5 pre-exposure (p = 0.008). In 189 patients with IVF-achieved pregnancies, pregnancy loss and hospital admissions did not differ between exposed and non-exposed groups. IVF treatment outcomes and the rate of early pregnancy loss appears to be unaffected by SARS-CoV-2 disease, despite a minor decline in sperm concentration among recent recoverees.

The contribution of mitochondrial function to reproductive aging.

PURPOSE: The number of women attempting to conceive between the ages of 36 and 44 has increased significantly in the last decade. While it is well established that women's reproductive success dramatically declines with age, the underlying physiological changes responsible for this phenomenon are not well understood. With assisted reproductive technologies, it is clear that oocyte quality is a likely cause since women over 40 undergoing in vitro fertilization (IVF) with oocytes donated by younger women have success rates comparable to young patients. Apart from oocyte donation, there is no known intervention to improve the pregnancy outcome of older patients. The aim of this paper was the review the relevant data on the potential role of mitochondria in reproductive aging. METHOD: Review of current literature on the subject. RESULTS: We present the current evidence that associate mitochondrial dysfunction with age related decrease in female reproductive outcome. CONCLUSIONS: The aging process is complex, driven by a multitude of factors thought to modulate cellular and organism life span. Although the factors responsible for diminished oocyte quality remain to be elucidated, the present review focuses on the potential role of impaired mitochondrial function.

The relationship between cannabis use and IVF outcome-a cohort study.

BACKGROUND: The effects of cannabis use on male and female reproduction have been the focus of scientific research for decades. Although initial studies raised concerns, more recent studies were reassuring. Considering the recent legalization of recreational use of cannabis in Canada, we sought to analyze IVF outcomes among users and non-users in a single IVF center. METHODS: This is a retrospective cohort study from a single IVF center assessing IVF outcomes among male-female, non-donor IVF patients that are either cannabis users or non-users. We analyzed the ongoing pregnancy rate as well as oocyte yield, fertilization rate, peak serum estradiol, sperm, and embryo quality. We used the Mann-Whitney test, chi-square test, and Kruskal-Wallis tests where appropriate. RESULTS: Overall, the study included 722 patients of which 68 (9.4%) were cannabis users, most defined as light users. The results of the study show similar implantation rate (40.74% vs. 41.13%) and ongoing pregnancy rate (35.2% vs. 29.1%) between the users and non-users, respectively. No significant difference between users and non-users in any of the other analyzed outcomes could be detected. CONCLUSIONS: The results may provide some reassurance for the lack of any demonstrable detrimental effects of cannabis consumption on IVF outcomes. This study was limited by its retrospective nature, self-reporting of cannabis use, and a small user sample size. A larger prospective study is needed to validate its findings.

Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients.

The aim of this work was to study gene expression patterns of cultured cumulus cells from lean and overweight-obese polycystic ovary syndrome (PCOS) patients using genome-wide oligonucleotide microarray. The study included 25 patients undergoing in vitro fertilization and intra-cytoplasmic sperm injection: 12 diagnosed with PCOS and 13 matching controls. Each of the groups was subdivided into lean (body mass index (BMI) < 24) and overweight (BMI > 27) subgroups. The following comparisons of gene expression data were made: lean PCOS versus lean controls, lean PCOS versus overweight PCOS, all PCOS versus all controls, overweight PCOS versus overweight controls, overweight controls versus lean controls and all overweight versus all lean. The largest number of differentially expressed genes (DEGs), with fold change (FC) |FC| >or= 1.5 and P-value < 0.01, was found in the lean PCOS versus lean controls comparison (487) with most of these genes being down-regulated in PCOS. The second largest group of DEGs originated from the comparison of lean PCOS versus overweight PCOS (305). The other comparisons resulted in a much smaller number of DEGs (174, 109, 125 and 12, respectively). In the comparison of lean PCOS with lean controls, most DEGs were transcription factors and components of the extracellular matrix and two pathways, Wnt/beta-catenin and mitogen-activated protein kinase. When comparing overweight PCOS with overweight controls, most DEGs were of pathways related to insulin signaling, metabolism and energy production. The finding of unique gene expression patterns in cumulus cells from the two PCOS subtypes is in agreement with other studies that have found the two to be separate entities with potentially different pathophysiologies.

Oxytocin augmentation in grandmultiparous parturients: to give or not to give?

OBJECTIVE: The present editorial was aimed to determine policies toward the use of oxytocin for labor augmentation among grandmultiparous (above 5 deliveries) parturients (GMPs). STUDY DESIGN: A questionnaire regarding attitudes toward oxytocin augmentation during labor among GMPs was distributed to all chairpersons of Ob/Gyn departments throughout the country; 20/23 chairpersons responded to the national survey. RESULTS: In all, 85% (17/20) of the chairpersons allowed the use of oxytocin for augmentation of labor in GMPs. Those answering positively to this question did not choose to limit the use of oxytocin for any level of parity. Moreover, 58% (11/19) of them did not obligate the concurrent use of intrauterine pressure catheter while using oxytocin augmentation in these patients. Only 22% (4/18) of the medical centers surveyed limited the maximal dose of Oxytocin among GMPs. The limited dose of oxytocin ranged from 8 to 16 micro/min. Alternatives for oxytocin augmentation in GMPs were breast stimulation (30%), and surgical induction (15%). Nevertheless, 50% of the chairpersons found no other suitable alternative for labor augmentation among GMPs. CONCLUSION: Oxytocin seems like an accepted method for labor augmentation among grandmultiparous women. Moreover, the vast majority of chairpersons did not mandate additional safety measures such as internal uterine catheter or limited dose regimens in these patients.

Co-Enzyme Q10 Supplementation Rescues Cumulus Cells Dysfunction in a Maternal Aging Model.

Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 are significantly lower than in those younger, both naturally and with assisted reproduction. Fertility decline is, in part, due to an increase in oocyte aneuploidy that leads to a reduced embryo quality, as well as an increased incidence of miscarriages and birth defects. Here we show that aging-associated malfunction is not restricted to the oocyte, as cumulus granulosa cells also display a series of defects linked to mitochondrial activity. In, both, human and mouse model, a decline in cumulus cell function due to increased maternal age is accompanied by a decreased expression of enzymes responsible for Coenzyme Q (CoQ) production, particularly Pdss2 and CoQ6. In an aged mouse model supplementation with Coenzyme Q10-a potent stimulator of mitochondrial function-restored cumulus cell number, stimulated glucose uptake, and increased progesterone production. CoQ10 supplementation might, thus, improve oocyte and cumulus cells quantity and quality, by improving the mitochondrial metabolism in females of advanced maternal age.