Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF/ICSI: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the impact of ovarian endometriomas (OMA) on indirect markers of oocyte quality in patients undergoing IVF, compared with women without anatomical or functional ovarian abnormalities. The search spanned original randomized controlled trials, case-control studies and cohort studies published in MEDLINE, the Cochrane Controlled Trials Register and the ClinicalTrials.gov database up to October 2023. Thirty-one studies were included in the meta-analysis, showing no significant differences in fertilization (OR 1.10, 95% CI 0.94-1.30), blastulation (OR 0.86, 95% CI 0.64-1.14) and cancellation (OR 1.06, 95% CI 0.78-1.44) rates. However, patients with OMA exhibited significantly lower numbers of total and mature (metaphase II) oocytes retrieved (mean difference -1.59, 95% CI -2.25 to -0.94; mean difference -1.86, 95% CI -2.46 to -1.26, respectively), and lower numbers of top-quality embryos (mean difference -0.49, 95% CI -0.92 to -0.06). The Ovarian Sensitivity Index was similar between the groups (mean difference -1.55, 95% CI -3.27 to 0.18). The lack of data published to date prevented meta-analysis on euploidy rate. In conclusion, although the presence of OMA could decrease the oocyte yield in patients undergoing IVF/intracytoplasmic sperm injection, it does not appear to have an adverse impact on oocyte quality.

Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency.

PURPOSE: To assess the feasibility and outcomes of oocyte cryopreservation with in vitro maturation (IVM) in post-pubertal girls undergoing fertility preservation (FP) for primary ovarian insufficiency (POI) risk. METHODS: Ovarian stimulation was performed with an antagonist protocol or progesterone priming. Ultrasound monitoring was performed transabdominally. Oocytes were retrieved transvaginally under IV sedation. Immature oocytes were subjected to IVM for up to 36 h. All MII oocytes were vitrified. The main outcome measure was the total number of mature oocytes cryopreserved. The secondary outcome was the increase in the mature oocyte yield after IVM. RESULTS: Indications for FP included mosaic Turner syndrome (mTS; n = 10), malignancy (n = 3), and POI risk (n = 2). The mean ± SD age, antral follicle count (AFC), and AMH levels were 14.2 ± 1.4 years, 8 ± 5.2 and 1.3 ± 1.3 ng/mL. In girls with mTS, the ovarian reserve was low for age (AFC 7.4 ± 4.7 and AMH 1.4 ± 1.6 ng/mL). Oocyte cryopreservation was possible in all girls with a range of 1-27 mature oocytes obtained, even in those who were previously exposed to chemotherapy or with low ovarian reserve, and no surgical complications were encountered. After IVM, the median mature oocyte yield increased significantly from 7.5 to 10.5 (p = 0.001). CONCLUSIONS: Oocyte cryopreservation appears to be feasible and safe in girls as young as 12 years of age at risk for POI The utility of IVM increases the yield of cryopreserved mature oocytes. Prior exposure to chemotherapy or low ovarian reserve should not be an automatic reason to exclude these girls from FP consideration.

Outcomes of random-start letrozole protocol with PGT-A in women with breast cancer undergoing fertility preservation.

PURPOSE  : To compare the cycle characteristics and outcomes of random-start-controlled ovarian stimulation (RSCOS) protocols to the outcomes of standard-start-controlled ovarian stimulation (SSCOS) cycles and to report the utility of PGT-A in these cycles. METHODS: One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. RESULTS: A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6 IU; P < 0.001), the mean number of mature oocytes and embryos was similar to SSCOS. However, there was a trend for a higher number of mean embryos with luteal start RSCOS (6.9 ± 2.7 in late follicular start vs. 9.4 ± 4.2 in luteal start, P = 0.08). PGT-A was performed in 48% of the cases that underwent embryo cryopreservation in RSCOS (12 women, mean age = 35.3 ± 4.1; 87 blastocysts), revealing a euploidy rate of 36.2 ± 22.3% per patient. This rate was comparable to a 45% aneuploidy rate from similarly aged published data. Of the 7 RSCOS patients who returned for frozen embryo transfer, 5 delivered and one has an ongoing pregnancy, while in SSCOS, 18 out of 40 cycles resulted in live birth. CONCLUSION: Our data suggests that RSCOS fertility preservation cycle outcomes are similar to those with SSCOS and result in age-appropriate euploidy rates.

The step-up protocol increases clinical pregnancy rates compared with the step-down in patients with unexplained infertility. A randomized controlled trial.

OBJECTIVE: Unexplained infertility is a relevant indication for controlled ovarian stimulation associated to intrauterine insemination. The "step-up" and "step-down" gonadotropin-based protocols were designed to reduce multiple pregnancy and ovarian hyperstimulation syndrome in polycystic ovary syndrome patients, but there is no related evidence in normoovulatory women undergoing intrauterine insemination. Our aim was to compare the efficacy and safety of both protocols with intrauterine insemination in unexplained infertility patients. METHODS: Randomized clinical trial including 145 women with unexplained infertility randomly following the step-up (n=73) or step-down (n=72) protocol. In the step-up group, patients started on day 3 of a spontaneous cycle administrating recombinant FSH 75IU sc/day, increasing it to 150IU if no response after 7 days. In the step-down, patients started administrating 150IU sc/day, constantly decreasing it to 75IU after 5 days. Recombinant hCG was administered when a follicle reached ≥18mm diameter. RESULTS: Clinical pregnancy rate was higher in the step-up group than in the step-down (20.5% vs . 8.3%; p =0.037). Significant differences between step-up and step-down protocols were found regarding days of rFSH administration (8.83±4.01% vs . 7.42±2.18%; p =0.001) and cancellation rate due to hyper response (8.21% vs . 25%; p =0.05). No differences were detected in miscarriage rates, multiple pregnancy rates/cycle and hyper stimulation syndrome incidence. CONCLUSIONS: The step-up protocol is longer-lasting but more effective obtaining pregnancies than the step-down in patients with unexplained infertility undergoing intrauterine insemination. This effect could be explained by lower cancellation rates due to ovarian hyper response than the step-down protocol, with no differences in ovarian hyper stimulation syndrome incidence.

Parental chromosomal heteromorphisms are not associated with an increased risk of embryo aneuploidy.

OBJECTIVE: Although chromosomal heteromorphisms are commonly found in the general population, some researchers have suggested a correlation with higher rates of embryo aneuploidy. This study aimed to assess the rates of embryo aneuploidy in couples who carry a chromosome heteromorphism. METHODS: The study included couples who had G-banding karyotype testing and underwent an IVF/PGT-A cycle between January 2012 and March 2018. The participants were classified by couple karyotype: Group A: ≥1 patient reported to be a heterochromatic variant carrier; Group B: both partners reported to be "normal". We assessed the rates of aneuploidy among the groups. We ran a multivariate regression analysis to assess the relationship between heterochromatic variants and the rates of embryo aneuploidy. RESULTS: Of the 946 couples analyzed, 48 (5.0%) reported being a carrier of ≥1 heterochromatic variant. We had 869 IVF/PGT-A cycles included in the analysis (Group A: n=48; Group B: n=82). There were no significant differences in embryo ploidy rates among the groups. The heterochromatic chromosome variant was not associated with increased likelihoods of aneuploidy (OR=1.04, CI:95% 0.85- 1.07; p=0.46). Finally, the gender of the heterochromatic variant carrier had no association with increased likelihood of aneuploidy (OR 1.02, CI 95% 0.81-1.28, p=0.82). CONCLUSIONS: Our study showed no association between parental heterochromatic chromosome variants and subsequent embryo aneuploidy rates. Ploidy rates do not appear to be negatively associated with couples when at least one patient is reported to be a carrier of a heterochromatic variant on the karyotype.