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.
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 stepup 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 stepup 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 stepdown 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.
Study question Is oocyte competence affected in patients with ovarian endometriosis in IVF/ICSI cycles? Summary answer In IVF cycles ovarian endometrioma negatively impacts oocyte quality in terms of oocytes and mature (MII) oocytes retrieved but not the fertilization and blastulation rates. What is known already Is still controversial whether the presence of a non-surgically treated ovarian endometrioma alone may adversely affect the oocyte quality in IVF/ICSI treatments. As oocyte quality is well reflected by the ability to complete maturation and undergo successful fertilization, the best clinical markers of oocyte competence are represented by number of MII oocytes retrieved and fertilization rates. Even though women with endometriomas had fewer oocytes and MII oocytes retrieved than women without, no further differences in reproductive outcomes have been found. The most recent meta-analysis, however, has serious limitations, such as clinical heterogeneity of the studies and a small sample size. Study design, size, duration A systematic review and meta-analysis of studies evaluating clinical markers of oocyte competence in women with ovarian endometriosis were conducted. Electronic searches were performed in PubMed, Cochrane database, and ClinicalTrials.gov up to December 2022. Randomized controlled trials and observational studies were eligible for inclusion. The risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Participants/materials, setting, methods Studies reporting ART outcomes among women with endometrioma were included. The main outcomes were clinical markers of oocyte competence including the number of oocytes retrieved, MII oocytes retrieved, ovarian sensitivity index (OSI), fertilization and blastulation rates. Mean differences (MD) and odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random and fixed effects model. Main results and the role of chance Of 876 unique records identified, 30 studies met inclusion criteria, and 21 studies, totaling 5962 participants, were included in the meta-analysis. The results showed that significantly fewer oocytes retrieved (mean difference (MD) = -1.67; 95% confidence interval (CI), -2.46, -0.88; p = <0.0001; I2=92%; low quality) and MII oocytes (MD = -2.45; 95% CI, -3.23, -1.67; p = <0.0001; I2=86%; moderate quality) were observed in women with endometriomas compared with the control. However, the OSI (MD = -1.47; 95% CI, -3.74, 0.81; p = 0.21; I2=97%; very low quality), fertilization rate (Odds ratio (OR) = 1.04; 95% CI, 0.78, 1.39; p = 0.79; I2=93%; low quality) and blastulation rate (OR = 0.90; 95% CI, 0.66, 1.22; p = 0.51; I2=95%; low quality) were not significantly different between the groups. Limitations, reasons for caution Despite removing patients with previous surgeries and diverse stages of endometriosis, main outcomes showed significant heterogeneity. The unilaterality/bilaterality, size, and the general extent of endometriomas could cause this heterogeneity. The quality of evidence generated from our findings is low, mainly due to the factors mentioned above. Wider implications of the findings Our findings suggest that endometriomas do not hinder fertility chances, as fertilization and blastulation rates were not compromised. Due to the risk of ovarian damage, these results argue against endometrioma excision. Further clinical trials with adequately-powered sample sizes should focus on blastulation and euploidy rates to validate our findings. Trial registration number Not applicable
OBJECTIVE: Though proper validation studies are lacking, intraovarian PRP is widely being promoted as treatment to improves ovarian response in women with low functional ovarian reserve (LFOR). The objective of this prospective pilot study was, therefore, to compare in women of very advanced ages ovarian responses before and after a PRP procedure.MATERIALS AND METHODS: This study involved 2 distinct groups of patients, both characterized by very advanced age: Group 1 were women with LFOR but still regular menstrual cycles; Group 2 were LFOR patients but with irregular menstrual cycles or amenorrhea. All patients in both groups had undergone prior failed IVF cycles. Before receiving a PRP treatment all patients received at least 6 weeks of pre-supplementation with DHEA (25mg TID) and CoQ10 (1000mg/day). The patient's PRP was extracted from their own blood as previously reported, 1 and was in early follicular phase under ultrasound control injected into ovaries subcapsular in 5-10 needle insertions per ovary, with the patient under subconscious sedation. IVF cycles were initiated on day-2 of subsequent menstrual period with 450 IU of FSH and 150IU of hMG (different manufacturers). Primary study outcomes were AMH levels and oocyte numbers retrieved. This still ongoing study is registered at ClinicalTrials.gov as NCT04275700.RESULTS: In Group 1 (n¼28) average age was 45.3 AE 4.6 years. AMH pre-PRP 0.36 AE 0.6, post-PRP 0.45 AE 0.5 N.S.); Oocytes pre-PRP 1.99 AE 1.5, post-PRP 2.12 AE 1.4 (N.S.). Group 2 (n¼9) average age was 45.3 AE 6.1 years. AMH pre-PRP 0.13 AE 0.29 post-PRP 0.23 AE 0.4; (N.S.); Oocytes pre-PRP 1.62 AE 2.1, post-PRP 1.3 AE 1.2 (N.S).CONCLUSIONS: In here investigated 2 groups of patients PRP administration does not appear to have significantly affected ovarian reserve, as documented by unchanged AMH levels and similar oocyte yields before and after PRP.IMPACT STATEMENT: Widely promoted as a way of ''rejuvenating'' ovarian function, here reported results are disappointing and call for caution in using intraovarian PRP injections as routine treatment. They also strongly suggest that PRP will not improve IVF outcomes in older women with LFOR. Our center currently still pursues 3 distinct PRP studies, involving clearly defined patient groups, two involving prospective randomization of younger women (under and above age 40).
Study question Data on random start letrozole ovarian stimulation (RSL) in breast cancer patients is scant. We studied RSL outcomes from a single-center with fertility preservation expertise. Summary answer RSL appears to result in high oocyte and embryo/blastocyst yield, with an age-appropriate aneuploidy rate. What is known already With increasing utility of neoadjuvant chemotherapy regimens in breast cancer, young women have limited time to undergo fertility preservation (FP) by oocyte or embryo cryopreservation. Random start stimulation protocols were developed to complete an ovarian stimulation cycle in the shortest time possible before cancer patients started chemotherapy. In addition, letrozole protocols were developed to mitigate the potential risks of high estrogen levels during ovarian stimulation in breast cancer patients. Even though both random start and letrozole supplemented ovarian stimulation have been studied individually, there is limited data on combining both strategies in random start letrozole (RSL) protocols. Study design, size, duration We reviewed our records from 2014 to 2021. We included the first FP cycle of all breast cancer patients undergoing RSL ovarian stimulation for oocyte or embryo cryopreservation. Cancer stages were grouped as 0-4, 0 being ductal carcinoma in situ (DCIS). Twenty-eight cycles met the criteria. Main outcome measures were number of oocytes retrieved and embryos cryopreserved. Secondary outcome measures were fertilization, blastocyst, and euploidy rates for the embryo cryopreservation group. Participants/materials, setting, methods Ovarian stimulation began on cycle days 3-26 with letrozole 5 mg/day initiated simultaneously with rFSH. The rFSH dose was based on age and antral follicle counts (AFC). Oocyte maturation was triggered with leuprolide acetate, rhCG or both 35h prior to retrieval. Main results and the role of chance The mean age was 33.5±4.9 years (range 26-40) and BMI 22.3±2.9(18.4-30.3). The mean breast cancer stage at FP was 1.7±0.9 (0-4), with 42.3% being stage-I disease. 77% of cases were estrogen receptor positive. AMH was 2.7±2.4 (0.16-7.9) and AFC 18.5±8.9(4-42). Ovarian stimulation began on cycle-day 13.7±7.3(2-26). 15(54%) cycles were started in the follicular and 13(46%) in the luteal-phase. The mean total rFSH dose was 3880±1615.4 IU(1275-8325) with a stimulation length of 11.8±2.4 days(8-19). Mean oocytes retrieved were 16.4±6.9(1-36) with a maturity rate of 71.4±17.9%(35.7-94.4). From 13 patients, 10.4±4.7(1-22) oocytes were cryopreserved. Among the 15 patients proceeding to embryo cryopreservation, the fertilization rate was 96.9±6.8%(80-100), resulting in 7.1±4.4(1-15) embryos. 24 embryos were cryopreserved on day-3 and 82 as blastocysts. PGT-A was performed in 72% of the cases, with euploidy rate of 37.7±24.4%(0-63.6). There was no difference in oocyte or embryo yield between follicular and luteal start patients. Likewise, fertilization rates and euploidy rates were similar. The comparative results are summarized in Table 1. To date, two patients conceived utilizing cryopreserved embryos. Both pregnancies resulted in healthy term babies. Limitations, reasons for caution Though our report is one of the largest series of RSL, it can be strengthened with longer follow up that includes pregnancy outcomes in a greater proportion of patients. Wider implications of the findings This is the first detailed report of the RSL protocol utility with PGT-A results in a breast-cancer population. RSL appears to result in high oocyte-yield, fertilization, and blastocyst formation rates, with age-appropriate euploidy. Additionally, the outcomes appear to be similar between patients undergoing follicular and luteal phase start RSL. Trial registration number not applicable
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