In vitro maturation (IVM) of human immature oocytes: is it still relevant?

In vitro maturation (IVM) of human immature oocytes has been shown to be a viable option for patients at risk of ovarian hyperstimulation syndrome (OHSS), those seeking urgent fertility preservation and in circumstances where controlled ovarian stimulation is not feasible. Moreover, IVM techniques can be combined with ovarian tissue cryobanking to increase the chances of conception in cancer survivors. The clinical applications of IVM in the field of reproductive medicine are rapidly expanding and the technique is now classified as non-experimental. In contrast to conventional IVF (in vitro fertilization), IVM offers several advantages, such as reduced gonadotropin stimulation, minimal risk of ovarian hyperstimulation syndrome (OHSS), reduced treatment times and lower costs. However, the technical expertise involved in performing IVM and its lower success rates compared to traditional IVF cycles, still pose significant challenges. Despite recent advances, such as innovative biphasic IVM systems, IVM is still an evolving technique and research is ongoing to refine protocols and identify techniques to improve its efficiency and effectiveness. A comprehensive understanding of the distinct mechanisms of oocyte maturation is crucial for obtaining more viable oocytes through in vitro methods, which will in turn lead to significantly improved success rates. In this review, the present state of human IVM programs and future research directions will be discussed, aiming to promote a better understanding of IVM and identify potential strategies to improve the overall efficiency and success rates of IVM programs, which will in turn lead to better clinical outcomes.

Relationship between the follicular distribution pattern of polycystic ovaries and the degree of menstrual disturbance and serum sex steroid levels.

Objective: This study aimed to examine the associations between follicular distribution pattern (FDP) in polycystic ovaries and menstrual disturbances in women with infertility. Materials and Methods: A retrospective review of patients was performed (n=73). Ultrasound images from cycle day 2-5 of a spontaneous or progestin induced menstrual cycle were reviewed. Ovaries were classified as polycystic ovarian morphology (PCOM) if they contained ≥12-follicles measuring 2-9 mm in diameter. Images of PCOM ovaries were classified as having a peripheral cystic pattern (PCP) with follicles arranged at the periphery of the ovary, or general cystic pattern (GCP) if follicles were dispersed heterogeneously throughout the ovarian stroma. Menstrual disturbance was assessed by questionnaire, and oligomenorrhea was defined as cycles >35 days in length. Results: PCP was more strongly associated with menstrual irregularity that GCP. 94% of subjects with bilateral PCP-experienced oligomenorrhea compared with 65% of women with a unilateral PCP ovary [odds ratio (OR) 9; p<0.05]. 29% of women with bilateral GCP ovaries experienced menstrual disturbances, less than bilateral PCP (OR 36; p=0.002), but similar to unilateral PCP (OR 3; p=0.07). Serum testosterone and luteinizing hormone (LH) levels were significantly correlated with the ovarian FDP. Conclusion: There is a relationship between menstrual irregularity or certain types of serum steroids and ovarian morphology. It remains unknown if morphology, testosterone or LH causes the menstrual disturbance or if they are co-initiated by an intervening factor.

Among high responders, is oocyte development potential different in Rotterdam consensus PCOS vs non-PCOS patients undergoing IVF?

PURPOSE: To evaluate the oocyte potential to develop to blastocyst in Rotterdam consensus PCOS in women with hyper-responses requiring freeze-all embryos. METHODS: Retrospective, single-academic center, cohort study of 205 patients who underwent freeze-all antagonist IVF cycles for OHSS risk between 2013 and 2019. Women in the PCOS group (n = 88) were diagnosed per the 2003 Rotterdam criteria. Control patients (n = 122) had no evidence of hyperandrogenism or menstrual disturbance. Data was compared by t-tests, chi-squared tests, or multivariate logistic regression (SPSS). Frozen blastocysts were Gardner's grade BB or better. RESULTS: There was no difference in terms of number of oocytes collected (PCOS vs non-PCOS 27.7 ± 9.4 vs 25.9 ± 8.2, p = 0.157), number of MII (20.7 ± 8.0 vs 19.1 ± 6.6, p = 0.130), number of 2PN fertilized (15.6 ± 7.4 vs 14.4 ± 5.9, p = 0.220), and number of frozen blastocysts (7.8 ± 4.9 vs 7.1 ± 3.8, p = 0.272). In addition, fertilization rates (74 ± 17% vs 75 ± 17%, p = 0.730), blastulation rates per 2PN (51 ± 25% vs 51 ± 25%, p = 0.869), and blastulation rates per mature oocytes (37 ± 18% vs 37 ± 15%, p = 0.984) were all comparable between PCOS and controls, respectively. Moreover, there was no difference when comparing PCOS and controls in pregnancy rates (45/81 vs 77/122, p = 0.28) and clinical pregnancy rates (34/81 vs 54/122, p = 0.75), respectively. Multivariate logistic regression controlling for confounders failed to alter these results. CONCLUSION: PCOS subjects do not seem to have altered oocyte potential as measured by number of MII oocytes collected, fertilization, and blastulation rates when compared to high-responder controls, with similar magnitude of stimulation.

How long can oocytes be frozen with vitrification and still produce competent embryos? A series of six cases.

Cryopreservation of oocytes is a relatively new and valuable option for fertility preservation. The duration since vitrification of embryos may be associated with a lower likelihood of success. We do not know how long the oocytes can be vitrified to produce viable pregnancies. We present six cases in which oocytes were vitrified for >10 years for social freezing or cancer. Two patients returned after 11 years, one after 12 years, and one returned after 13 years to use their vitrified oocytes for pregnancy. Four singleton live births were recorded. The two remaining patients returned after 13 years and again after 14 and 15 years, respectively, and failed to conceive. This has raised the burden of the literature on oocyte vitrification for more than 10 years. Oocyte vitrification is an effective option for long-term fertility preservation in women.

Is There an Association Between Sperm Parameters and Sexual Orientation? A Cross Sectional Study.

OBJECTIVE: To evaluate whether sexual orientation affects sperm parameters. METHODS: This was a cross-sectional study using existing data from an academic reproductive centre for the period of April 01, 2009, to March 31, 2021. We compared the results of sperm analysis from male patients who were in same-sex relationships (study group) with those of men in heterosexual relationships who did not have male-factor infertility (control group). A subsequently comparison of both groups with World Health Organization (WHO) reference values was also performed. RESULTS: Thirty-nine samples from the study group were compared with 494 samples from the control group. All parameters, apart from morphology, were comparable. The median sperm concentrations were 64 (interquartile range [IQR] 32.1-102.9) million/mL and 50.1 (IQR 25.3-92.5) million/mL in the study and control groups, respectively (P = 0.252), whereas the median percentage of progressive motile sperm was 50% (IQR 34-65) in the study group and 52% (IQR 33-65) in the control group (P = 0.198). The median percentage of morphologically normal sperm was higher in the control group than in the study group (6% vs. 5%; P = 0.019). However, no significant difference was found when sperm morphology was dichotomized with the cut-off of ≥4% (74.1% and 74.4%, respectively; P = 0.966). When compared with the WHO reference group, the percentage of men with total motile sperm counts ≥10 million and the percentage of men with normal morphology were significantly lower in both groups. CONCLUSION: Our study suggests that there is no relationship between sexual orientation and sperm parameters.

MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†.

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it colocalizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed toward the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.

Influence of Maternal Age and Ovarian Reserve on the Decision to Continue or to Cancel IVF Cycles in Patients with One or Two Large Follicles: a Dual Effect.

This study aimed to study whether IVF stimulation that results in one or two mature follicles should proceed to oocyte retrieval. This is a retrospective cohort study conducted at McGill University Health Center on 459 patients who underwent IVF treatment between 2011 and 2014, undergoing hormonal stimulation and monitoring of their ovarian response. The primary outcomes were pregnancy and live birth rates. Statistical modeling was used to determine individual roles of patient age and ovarian reserve on outcomes, while controlling for the other factors. Of the 459 cycles included in the study, 360 cycles (78.4%) ended in embryo transfer. Live birth rates per cycle were 15.6%, for the ≤ 34-year-olds; 6.5%, for the 35-39-year-olds; and 2.7%, for the ≥ 40-year-olds (p < 0.01). Twenty-five percent of the cycles in the ≥ 40-year-old group were canceled versus 17% and 15% in the 35-39-year-old and ≤ 34-year-old groups, respectively (p < 0.05). Testing likelihood of live birth as a function of age and antral follicular count (AFC) revealed that a 1-year increase in age reduces the likelihood of live birth by 11% (p < 0.05) and one-unit increase in AFC count leads to a 9% increase in the odds of a live birth (p < 0.05). For the youngest age group, the AFC had a most significant effect, and those with AFC > 11 had 56% live birth rate, while those with AFC ≤ 11 had only 6% of live birth rate. This study supports a shift in reasoning from age being the predictor of outcomes in women with a low response at IVF to both age and ovarian reserve needing to be taken into consideration.

Hope for male fecundity: clinically insignificant changes in semen parameters over 10 years at a single clinic while assessing an infertility population.

PURPOSE: What is the trend in sperm parameters in a group of men attending a single reproductive center, over a 10-year period? METHODS: A retrospective study was conducted on 12,188 semen samples obtained from unique individuals who attended a university reproductive clinic from 2009 to 2018, inclusively. Semen analysis was done using computer-assisted sperm analysis and verified by an andrologist. Analysis was done after dividing the dataset into two groups: above WHO 2010 lower reference limits (ARL) (N = 6325) and below the reference limits (BRL) (N = 5521). RESULTS: Volume increased slightly (ARL, p = 0.049) before returning to baseline or was stable (BRL, p = 0.59). Sperm concentration and total count of the BRL and ARL group declined initially and then recovered slightly (p < 0.0001, in all cases). Although these changes were statistically significant, this was due to the large study population; clinically, these changes were quite mild and would not have been significant for fertility. Sperm total motility and progressive motility of both the BRL group and the ARL group increased slightly from 2009 until 2015 and then decreased back to baseline (p < 0.0001). This change offset the decrease in count seen in those years. A spurious change was observed with sperm morphology that declined after the first 2 years and remained stable thereafter (p < 0.0001, in both groups). However, this change was attributed to a contemporaneous change in the method of analyzing strict morphology which happened when the change occurred. CONCLUSION: While statistically significant changes were found, clinically, these changes were quite mild and would not have been significant for fertility.

Effect of double embryo transfer derived from autologous frozen oocytes on multiple pregnancy rates and presentation of success rates stratified by age at retrieval

Objective: To compare outcomes transferring one or two embryos in autologous frozen oocyte cycles. Material and Methods: A retrospective cohort study conducted at an academic fertility center between January 2012 and December 2018. One-hundred and fourteen patients underwent frozen oocyte transfers; 67 single embryo transfer (SET) and 47 double embryo transfer (DET). No subjects had more than two embryos transferred. Data were analyzed using t-test and chi-squared testing. Multivariate logistic regression was used to control for confounding effects. Power analysis suggested an 82% power with alpha of 5% and effect size of 27%. Results: Regarding the embryo stage, 72% were cleavage embryos and 28% were blastocyst embryos. Among those who had cleavage stage embryos, 48.8% underwent SET and 51.2% underwent DET. In the blastocyst embryos group these proportions were 84.4% and 15.6%, respectively. There were no difference in pregnancy rate for SET (40.3%) vs DET (36.2%) (p=0.78). Additionally, the live birth rate did not differ between SET and DET (28.4 vs 19.1%, respectively, p=0.26). The multivariate multilevel analysis provided adjusted odds ratios (95% confidence interval) of: 1.85 (0.46-7.44) for pregnancy; 0.497 (0.05-4.86) for clinical pregnancy; and 0.82 (0.11-6.29) for live birth when comparing SET and DET. Multiple pregnancy rates were significantly lower in the SET (0%), compared with DET group (44.4%) (p<0.002). Conclusion: SET results in excellent live birth outcomes in autologous frozen oocyte cycles. However DET results in significantly increased rates of multiple pregnancies. This suggests that SET is a viable option in autologous frozen oocyte cycles.

Polybrominated Diphenyl Ethers in Human Follicular Fluid Dysregulate Mural and Cumulus Granulosa Cell Gene Expression.

Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants incorporated into numerous consumer products, leach out into dust resulting in widespread exposure. There is evidence from in vitro and in vivo animal studies that PBDEs affect ovarian granulosa cell function and follicular development, yet human studies of their association with female infertility are inconclusive. Here, we tested the hypothesis that exposure to the PBDEs in follicular fluid is associated with dysregulation of gene expression in the mural and cumulus granulosa cells collected from women undergoing in vitro fertilization by intracytoplasmic sperm injection. The median concentration of the ∑ 10PBDEs detected in the follicular fluid samples (n = 37) was 15.04 pg/g wet weight. RNA microarray analyses revealed that many genes were differentially expressed in mural and cumulus granulosa cells. Highest vs lowest quartile exposure to the Σ 10PBDEs or to 2 predominant PBDE congeners, BDE-47 or BDE-153, was associated with significant effects on gene expression in both cell types. Mural granulosa cells were generally more sensitive to PBDE exposure compared to cumulus cells. Overall, gene expression changes associated with BDE-47 exposure were similar to those for ∑ 10PBDEs but distinct from those associated with BDE-153 exposure. Interestingly, exposure to BDE-47 and ∑ 10PBDEs activated the expression of genes in pathways that are important in innate immunity and inflammation. To the best of our knowledge, this is the first demonstration that exposure to these environmental chemicals is associated with the dysregulation of pathways that play an essential role in ovulation.

Blastocyst morphology has no relationship with serum ß-hCG levels and live birth rates once pregnant.

OBJECTIVE: What is the role of blastocyst morphology on day16 ß-hCG serum levels and pregnancy outcomes among patients who conceived through IVF cycles with single fresh Gardner's scored blastocyst transfers. STUDY DESIGN: A retrospective cohort study conducted at a single academic fertility center between January 2013 and December 2017. A total of 643 pregnancies were included in the study. RESULTS: The patients were divided into 5 groups according to Gardner's blastocysts grade of the ICM and the TE (grade), and into 4 groups according to blastocyst Gardner's degree of blastocoel expansion (stage). No significant differences were found between the different morphologic groups and day16 ß-hCG serum levels, clinical pregnancy rates and live births. A weak significant correlation was observed between Gardner's blastocysts grade and day 16 ß-hCG (Correlation Coefficient r= -0.098, p = .014) this correlation remained significant after controlling for confounders. (r= -0.099 p = . 013). A weak significant correlation was observed between Gardner's stage and day 16 ß-hCG (Correlation Coefficient r = 0.086, p = 0.029) this correlation lost significance after controlling for confounders. (r = 0.055, p = 0.340). When evaluating predictors of live birth using multivariate logistic regression, blastocyst grade (p = 0.33) and stage (p = 0.65), at transfer, were not associated with live births, when controlling for confounding effects. CONCLUSION: Once the patient conceives after IVF with single blastocyst, none of the morphological parameters have a strong impact on the day16 serum level of ß-hCG. Among women who conceived, blastocyst grade and stage were not associated with live births.

The biochemical pregnancy loss rate remains stable up irrespective of age and differs in pattern from clinical miscarriages.

INTRODUCTION: As women age, the increasing rate of aneuploidy lead to an augmentation in the incidence of clinical miscarriages. It was anticipated that biochemical pregnancy rates would also rise with maternal age. However, no study has previously evaluated the effect of maternal age on biochemical pregnancy rates. MATERIAL AND METHODS: A retrospective cohort study of 2177 subjects who underwent single embryo transfer (SET) as part of a fresh or thawed IVF cycle were recruited from 2008 through 2012, resulting in 952 pregnancies. Data was stratified for age and compared using analysis of variance (continuous data) and chi-squared tests (categorical data). RESULTS: The likelihood of a clinical miscarriage increased with age (p < .001). Surprisingly, advancing age had no effect on the biochemical pregnancy loss rate (p = .72) (Age 21-30 y: 10.7%, Age 31-35 y:9.8%, Age 36-40y:11.5%, Age 41-42 y:13.6%). CONCLUSIONS: Biochemical pregnancy loss rate did not increase as a function of age in women 21 to 42 years of age.

What Are the Live Birth and Multiple Pregnancy Rates When 1 Versus 2 Low-Quality Blastocysts Are Transferred in a Cryopreserved Cycle? a Retrospective Cohort Study, Stratified for Age, Embryo Quality, and Oocyte Donor Cycles.

Outcomes among women who transferred only Gardner's grade BB or lower quality frozen embryos transferred (FET) are not well known. Our objective is to study whether transferring 2 versus 1 frozen low-quality blastocysts will increase the live birth rate (LBR) and the multiple pregnancy rate (MPR). This is a retrospective cohort study including 1104 FET cycles. Only day 5-6 blastocysts of grade BB or lower quality were included. Clinical pregnancy rate (CPR), MPR, and LBR per cycle were compared between single embryo transfer (SET) (n = 969) and double embryo transfer (DET) (n = 135). CPR and MPR were compared between SET and DET in grade BB, BC, CB, and CC individually. Among SET, BB blastocysts had higher CPR 34% (P = 0.0001) and a sub-significant increase in LBR 19% (P = 0.059) in comparison to other grade SET. Among all BB, MPR was significantly higher when transferring two versus one (5.9 vs. 1.9, P = 0.009). If age at egg collection ≥ 40 years (n = 97), no difference was found in CPR (11.1 vs. 11.7, P = 0.9), MPR (0 vs. 0), and LBR (6.3 vs. 0,P = 0.13) when SET or DET was performed. If age was < 40 years (n = 818), the MPR was significantly higher in DET than SET (6.7 vs. 1.63, P = 0.004). In egg donor cycles (n = 189), there was no difference in CPR, MPR, and LBR between SET and DET. Single embryo transfer should be offered even in women ≥ 40 years of age or transferring lower quality embryos since transferring more did not increase outcomes in this group, and SET is likely the safest path.

An age-based sperm nomogram: the McGill reference guide.

STUDY QUESTION: How does age affect various semen parameters? SUMMARY ANSWER: For most semen parameters, the nomogram of the entire population was biphasic, peaking around the fourth decade of life. WHAT IS KNOWN ALREADY: In clinical practice, semen quality is examined by using the WHO 2010 reference limits but these limits do not account for male age. A percentile-based, large-scale nomogram describing how different semen parameters change throughout reproductive life has been lacking. STUDY DESIGN, SIZE, DURATION: A retrospective study was conducted with 12 188 sperm samples, obtained from individuals who attended the McGill University Health Centre reproductive clinic between 2009 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: One sample from each individual who attended the clinic during the study period was analysed by using computer-assisted sperm analysis (CASA). The analysed parameters were human-verified and included sperm concentration, motility, progressive motility, total count, morphology and semen volume. Based on this analysis, the entire dataset (n = 12 188) was further divided into two groups of samples: samples that surpassed the WHO 2010 lower reference limits ('above reference limits' group, ARL; n = 6305), and samples that did not ('below reference limit' group, BRL; n = 5883). Regression quantiles were fitted as a function of age to generate age-dependent nomograms, and these quantiles were divided into 5th, 25th, 50th, 75th and 95th percentiles. MAIN RESULTS AND THE ROLE OF CHANCE: In the entire dataset, age had a significant influence (P < 0.001) on all parameters (except morphology) which demonstrated a biphasic trend peaking in the fourth decade of life. In the ARL group, age had a significant influence (P < 0.01) on all semen parameters except sperm concentration and morphology. However, unlike in the entire dataset, only semen volume demonstrated a biphasic trend in the ARL group (peaking in the fourth decade of life), whereas other parameters either remained unchanged (concentration and morphology) or consistently declined with age (sperm motility, progressive motility and total sperm count). Percentile-based nomograms were generated for individuals between the ages of 20 and 60 years in the entire dataset and in the ARL group. LIMITATIONS, REASONS FOR CAUTION: First, the semen samples were obtained from individuals who were referred to a fertility clinic, such that the entire dataset does not necessarily represent the general population. Second, the cross-sectional sampling design increases variance, and the nomograms are less accurate in the 5th and 95th percentiles and at the extremes of the age distributions. Third, the observed age-dependent changes in semen parameters do not necessarily indicate changes in fertility, as not all factors that affect male fertility were analysed. Fourth, some of our semen analyses employed CASA, which can have variability issues. Finally, our models did not incorporate possible secular trends. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first nomogram that correlates age with semen quality parameters in different population percentiles, thus complementing the current reference limits set by the WHO in 2010. Most examined semen parameters in our study changed non-linearly with age; therefore, age should be regularly employed as a factor in the clinical analysis of semen samples. STUDY FUNDING/COMPETING INTEREST(S): The authors have not received any funding to support this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Added Benefit of Immature Oocyte Maturation for Fertility Preservation in Women with Malignancy.

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.

A comparison of IVF outcomes transferring a single ideal blastocyst in women with polycystic ovary syndrome and normal ovulatory controls.

PURPOSE: To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst. METHODS: A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates. RESULTS: 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18-0.92). CONCLUSION: After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

Outcomes of Preimplantation Genetic Testing for Single Gene Defects in a Privately Funded Period and Publicly Funded Period: A North-American Single Center Experience.

BACKGROUND: The purpose of this study was to assess whether the outcomes from IVF-preimplantation genetic testing (IVF-PGT) cycles for single gene defects (SGD) (PGT-M) differ between a privately funded period (PRP) and publicly funded period (PUP). METHODS: A retrospective cohort study was conducted in a North-American single tertiary center. The PRP (March 1998 to July 2010) comprised 56 PGT-M cycles from 58 IVF cycles in 38 couples, and the PUP (August 2010 to May 2015) comprised 59 PGT-M cycles from 87 IVF cycles in 38 couples. One PGT-M cycle is defined as one biopsy procedure from one or serial IVF cycles. A p-value of 0.05 was considered statistically significant. RESULTS: The clinical pregnancy rates (CPR) per PGT-M cycle were 30.4% and 52.5% in each period, respectively (p=0.021). The live birth rates (LBR) per PGT-M cycle were 21.5% versus 40.9% in each period, respectively (p=0.037). A sub-analysis within the PUP comparing 39 PGT-M cycles from 39 IVF cycles with 20 PGT-M cycles from 49 IVF cycles yielded CPRs per PGT-M cycle of 64.1% and 30.0% and LBRs per PGT-M cycle of 53.8% and 15.0%, in each group, respectively (p< 0.05 for both). CONCLUSION: The transition from private to public funding and a single embryo transfer (ET) guideline has little impact on embryological and clinical outcomes of PGT-M cycles, and results in lower rates of multiple pregnancies. However, these two systems may serve different populations.

Human oocytes harboring damaged DNA can complete meiosis I.

OBJECTIVE: To determine whether human oocytes possess a checkpoint to prevent completion of meiosis I when DNA is damaged. DESIGN: DNA damage is considered a major threat to the establishment of healthy eggs and embryos. Recent studies found that mouse oocytes with damaged DNA can resume meiosis and undergo germinal vesicle breakdown (GVBD), but then arrest in metaphase of meiosis I in a process involving spindle assembly checkpoint (SAC) signaling. Such a mechanism could help prevent the generation of metaphase II (MII) eggs with damaged DNA. Here, we compared the impact of DNA-damaging agents with nondamaged control samples in mouse and human oocytes. SETTING: University-affiliated clinic and research center. PATIENT(S): Patients undergoing ICSI cycles donated GV-stage oocytes after informed consent; 149 human oocytes were collected over 2 years (from 50 patients aged 27-44 years). INTERVENTIONS(S): Mice and human oocytes were treated with DNA-damaging drugs. MAIN OUTCOME MEASURE(S): Oocytes were monitored to evaluate GVBD and polar body extrusion (PBE), in addition to DNA damage assessment with the use of γH2AX antibodies and confocal microscopy. RESULT(S): Whereas DNA damage in mouse oocytes delays or prevents oocyte maturation, most human oocytes harboring experimentally induced DNA damage progress through meiosis I and subsequently form an MII egg, revealing the absence of a DNA damage-induced SAC response. Analysis of the resulting MII eggs revealed damaged DNA and chaotic spindle apparatus, despite the oocyte appearing morphologically normal. CONCLUSION(S): Our data indicate that experimentally induced DNA damage does not prevent PBE in human oocytes and can persist in morphologically normal looking MII eggs.

Impact of extent and biochemical parameters of lymphoma on fertility preservation outcome.

OBJECTIVE: To evaluate the impact of lymphoma aggressiveness on ovarian response during fertility preservation treatment. DESIGN: Retrospective cohort study. SETTING: University-affiliated tertiary hospital. PATIENT(S): Women with lymphoma who underwent ovarian stimulation for fertility preservation in the period from 2009 to 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome: the number of mature oocytes; secondary outcomes: the number of retrieved oocytes, estradiol level, and number of follicles >14 mm on the day of oocyte maturation trigger. RESULT(S): Patients with stage I-II lymphoid neoplasms (localized disease) were compared with those with stage III-IV lymphomas (advanced disease). Women with favorable levels of biochemical prognostic markers were also compared with those with unfavorable levels. Women with favorable levels of biochemical prognostic markers (n = 74) had a higher number of mature oocytes compared with patients with unfavorable serum levels (n = 67): 11 (7.8-16) versus 9 (5-11), respectively. The number of mature oocytes was similar between patients with localized (n = 75) and advanced (n = 66) lymphomas. Women with unfavorable combination of stage and biochemical factors had lower number of mature oocytes compared to patients with favorable combination: 8 (5-10) versus 11 (7-16), respectively. Multivariate logistic regression showed that favorable levels of biochemical markers as well as a combination of extent and biochemical parameters were statistically significantly associated with the result of over 10 mature oocytes. CONCLUSION(S): Highly-aggressive lymphoid neoplasms have a negative impact on ovarian function and response during fertility preservation treatment.