Journal of Assisted Reproduction and Genetics最新文献

Purpose: To assess oocyte competence and embryo chromosomal constitution in phenotype-D PCOS women undergoing ICSI for PGT-A at the blastocyst stage.

Methods: Retrospective study at a private IVF center. In the period 2013-2021, 58 naïve phenotype-D PCOS women (i.e., oligomenorrhea, ovarian PCO-morphology, and absence of hyperandrogenism) underwent ICSI with ejaculated sperm for PGT-A. These cases were matched to 58 controls selected from 2211 naïve women with idiopathic infertility planned for the same treatment in the same period. The matching variables were age (≈ 36 years), BMI (≈ 22), cumulus oocyte complexes (COCs) retrieved (≈ 21-23), and sperm quality (≈ 43-45% men with all sperm parameters > 5th percentile). The primary outcome was euploid blastocyst rate (EBR) per cohort of inseminated oocytes.

Results: Maturation rates per COCs and euploidy per biopsied blastocysts were similar. PCOS patients with phenotype-D showed higher fertilization per inseminated oocytes and higher blastulation per zygotes. This resulted into a higher EBR per inseminated oocytes and more euploid blastocysts available for transfer, although these differences adjusted for confounders were not significant. The live birth rate per first euploid transfers was comparable, so were all other outcomes considered.

Conclusions: Oocyte competence was not compromised in phenotype-D PCOS women, while good prognosis idiopathic infertile women might have unknown oocyte issues. In case of repeated failures after intrauterine insemination, a timely referral to IVF might represent an efficient strategy, in line with the "one-and-done" approach fulfilling a family planning perspective. Indeed, 22% of the phenotype-D PCOS women had 2 singleton LBs and 76% had surplus oocytes/euploid blastocysts after achieving ≥ 1 live birth.

Purpose: To evaluate whether co-treatment of repeated GnRHa triggers with GnRH antagonist protocols can improve the clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) procedures.

Methods: In this retrospective study, 712 Chinese Han women aged 20-42 undergoing autologous IVF/ICSI-ET with a flexible GnRH antagonist protocol were analyzed. The 735 cycles were split into the single (n = 238) and the repeated (n = 497) GnRHa groups. In the single GnRHa group, 0.2 mg of triptorelin was given for oocyte maturation, whereas in the repeated GnRHa group, two doses of 0.2 mg were administered 12 h apart. PSM design was used for a fair comparison. The main study outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), good-quality embryo rate, and fertilization rate. Multivariate logistic regression analyses were used to identify all potential factors affecting clinical outcomes.

Results: Post-PSM, analysis of 159 cycles per group showed the repeated GnRHa group outperforming the single GnRHa group in IVF fertilization rates (71.5% vs. 67.7%, P < 0.05) and good-quality embryo rate (47.1% vs. 43.7%, P < 0.05). Furthermore, the repeated GnRHa group achieved higher CPR (72.6% vs. 53.4%, P < 0.05) and LBR (59.7% vs. 43.8%, P < 0.05) in FET cycles. Multivariate logistic regression indicated a significant negative correlation between the use of a single GnRHa trigger and both clinical pregnancy (OR = 0.382, P < 0.05) and live birth (OR = 0.518, P < 0.05).

Conclusion: Our study reported that individuals who received a repeated GnRHa trigger exhibited higher CPR and LBR during FET cycles compared to those who received a single dose GnRHa trigger.

Purpose: To elucidatethe epigenetic alteration associated with impaired oogenesis in endometrioma using multi-omic approaches.

Methods: ATAC-seq was performed on the granulosa cells (GCs) of 6 patients (3 with endometrioma and 3 without). Follicular samples from another 20 patients (10 with endometrioma and 10 without) were collected for mRNA-seq analysis of GCs and extracellular vesicles (EVs) of follicular fluid. qRT-PCR validated candidate genes in GCs from 44 newly enrolled patients (19 with endometrioma and 25 without). mRNA abundance was compared with the Mann-Whitney test. Pearson's correlation analyzed relationships between candidate genes and oocyte parameters.

Results: Chromatin accessibility and gene expression profiles of GCs from endometrioma patients differed significantly from the pelvic/tubal infertility group. RNA-seq revealed most differentially expressed genes were downregulated (6216/7325) and enriched in the cellular localization pathway. Multi-omics analyses identified 22 significantly downregulated genes in the GCs of endometrioma patients, including PPIF (P < 0.0001) and VEGFA (P = 0.0148). Both genes were further confirmed by qRT-PCR. PPIF (r = 0.46, p = 0.043) and VEGFA (r = 0.45, p = 0.048) correlated with the total number of retrieved oocytes.

Conclusions: GC chromatin remodeling may disrupt GC and EV transcriptomes, interfering with somatic cell-oocyte communication and leading to compromised oogenesis in endometrioma patients.

Purpose: To determine the genetic cause of infertility in two unrelated families of female patients suffering from oocyte degeneration and fertilization failure.

Methods: Whole exome sequencing and Sanger sequencing were performed to identify the disease-causing genes of infertility in two unrelated female patients. Minigene experiments were conducted to confirm the effect of splice site mutations on mRNA splicing.

Results: In two unrelated female infertility patients, a novel compound heterozygous splicing mutation (c.516-1G > T and c.877-1G > A) in PATL2 gene and a novel homozygous splicing mutation (c.1222-1G > A) in WEE2 gene were identified. Minigene splicing assays revealed that the c.516-1G > T mutation in PATL2 resulted in a deletion of 8 bases in mRNA that causes a frameshift (c.516-523delTCCCCCAG, p.P173Q fs*13). The c.877-1G > A mutation led to the skipping of exons 10 and 11 and retention of introns 8-9 in PATL2 mRNA. The c.1222-1G > A mutation resulted in the deletion of exon 9 in WEE2 mRNA, leading to an in-frame deletion of 57 amino acids in the WEE2 protein (p.408-464del).

Conclusion: Our study discovered novel splicing mutations in PATL2 and WEE2, further expanding the mutation spectrum of these two genes and providing guidance for genetic counseling and diagnosis of female infertility.

Purpose: To explore the effects of parental sex chromosome abnormality on their preimplantation embryos.

Methods: This is a retrospective cohort study including 83 couples with sex chromosome abnormalities undergoing preimplantation genetic testing (PGT) between 2013 to 2023. The preimplantation genetic testing results and pregnancy outcomes were compared to those of a control group consisting of 166 age-matched couples with normal karyotypes who underwent preimplantation genetic testing for monogenic disorders (PGT-M). Student's t-tests, chi-square or Fisher's exact tests were applied to compare clinical characteristics.

Results: The embryo euploidy rate was lower (58.94% vs 65.44%, P = 0.048, OR 0.76, 95%CI [0.58,0.99]) and the sex chromosomal aneuploidy rate was higher in the couples with sex chromosome abnormalities than control group (6.62% vs 2.63%, P = 0.004, OR 2.63, 95%CI [1.37,5.05]). The pregnancy outcomes including clinical pregnancy rates (48.57% vs 57.25%, P = 0.305) and live birth rates (47.14% vs 52.90%, P = 0.465) were similar between the two groups in their first embryo transfer cycles.

Conclusions: To avoid high risk of embryo aneuploidy and sex chromosome abnormalities, preimplantation genetic testing should be recommended to couples with sex chromosome abnormalities.

Purpose: With urbanization and industrialization process accelerated, humans are exposed more and more trace elements. This study aimed to explore the potential associations of trace elements with the outcomes of in vitro fertilization embryo transfer (IVF-ET).

Methods: Total 181 women who underwent IVF-ET were enrolled, among which 89 women underwent fresh ET after IVF. Trace elements were measured in the serum and follicular fluid (FF) samples by inductively coupled plasma-mass spectroscopy. The associations of the levels of different trace elements with IVF-ET outcomes, including normal fertilization, high-quality embryos, and clinical pregnancy (fresh ET) were analyzed.

Results: Twenty-five out of twenty-eight trace elements showed higher concentrations in the serum than those in the FF. Normal fertilization was positively associated with Cu and Mn in the FF. High-quality embryos was positively associated with Cu in the serum and FF, and Zn in the serum. Clinical pregnancy was positively associated with Ge in the serum, and inversely associated with Al, Ba, and Pb in the serum. Additionally, poor outcomes of IVF-ET should be noticed in women with FF level of Cu < 955.38 ng/mL, FF level of Mn < 3.42 ng/mL, serum level of Ge < 6.11 ng/mL, serum level of Al > 28.44 ng/mL, and serum level of Pb > 0.90 ng/mL.

Conclusions: IVF-ET outcomes were positively associated with Cu, Mn, Zn, and Ge, and inversely associated with Al and Pb. Properly controlling the exposure of relevant trace elements is necessary for patients with the need of IVF-ET.

Purpose: To determine whether patients with Marfan syndrome are at an increased risk for reproductive disorders.

Methods: This retrospective cohort study was conducted using the US collaborative network on the TriNetX research network of health care organizations. We included female patients aged 18-44 and identified a cohort of 4347 patients with Marfan syndrome (ICD-10 Q87.4). Our control cohort consisted of 16,424,990 patients without a diagnosis of Marfan syndrome or Ehlers-Danlos syndrome (ICD-10 Q79.6). The primary outcomes included gynecologic diagnoses such as dysmenorrhea and endometriosis, and our secondary outcomes included urogynecologic, fertility, and obstetric outcomes, all identified by ICD-10 codes. We conducted a relative risk analysis with a p-value of <0.05 considered significant.

Results: Patients with Marfan syndrome were at an increased risk for pelvic and perineal pain, dysmenorrhea, abnormal uterine bleeding, endometriosis (all p <0.0001), dyspareunia (p =0.0009), leiomyoma (p =0.0076), polyp of female genital tract (p =0.016), urinary incontinence (p <0.0001), female genital prolapse (p =0.0006), fertility testing (p =0.0075), cesarean delivery (p =0.0003), gestational hypertension (p =0.0012), and pre-eclampsia (p =0.0024) compared to the control group following an adjusted, matched comparison.

Conclusions: Patients with Marfan syndrome have an increased risk of numerous reproductive disorders and obstetric complications compared to patients without this diagnosis.

Purpose: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART.

Method: Taking advantage of an in vitro postovulatory oocyte aging model, we examined the morphological integrity and NAD⁺ levels of ovulated mouse MII oocytes after 24 h of culturing. Following in vitro fertilization, we assessed the embryonic developmental potential of oocytes affected by POA. Using immunofluorescence and confocal microscopy, we measured the levels of ROS, mitochondrial function, and γH2AX. We also evaluated spindle assembly and chromosome alignment. Additionally, we detected the distribution of cortical granules to assess the metabolic and quality changes in POA oocytes with the supplementation of NR. To further our analysis, quantitative real-time PCR was conducted to measure the mRNA expression levels of antioxidant enzymes Sod1 and Gpx1 in the oocytes.

Results: With 200 μM NR supplementation during in vitro culture for 24 h, the oocytes from POA demonstrated reduced signs of aging-related decline in oocyte quality, including reduced ROS accumulation, improved mitochondrial function, and corrected mis-localization of cortical granules. This improvement in oocyte quality is likely due to the inhibition of oxidative stress via the NAD⁺/SIRT1 signaling pathway, which also helped to restore normal spindle assembly and chromosome alignment, as well as reduce the elevated levels of γH2AX, thereby potentially enhancing the embryonic development potential.

Conclusion: Current research provides evidence that NR is an efficient and safe natural component that prevents the process of POA and is thus a potential ideal antiaging drug for raising the success rates of ART in clinical practice.

Purpose: Utilization of oocyte donation has become an increasingly common practice in assisted reproductive technology (ART). Since the introduction of larger carrier screening (CS) panels and extended family medical histories (EFMH), studies have not examined how this information factors into the oocyte donor selection process. This exploratory, qualitative study provides further insight into what role, if any, donors' available genetic information (e.g., larger CS panels and EFMH) plays in selecting an oocyte donor.

Methods: An online screening survey was distributed to individuals who have undergone or are currently in the process of selecting an oocyte donor through the RESOLVE network and Mayo Clinic's Reproductive Endocrinology and Infertility clinic. From 13 survey respondents, six oocyte recipients subsequently participated in semi-structured telephone interviews and discussed their experiences as oocyte recipients including their perceptions of donors' available genetic information and process in choosing an oocyte donor.

Results: Genetic information was seen as valuable and reassuring for participants, particularly EFMH, but did not play a significant role in the selection process for these participants. Supplemental emergent themes provide context on the psychosocial complexities of the oocyte recipient experience and possible explanations for why genetic information is not a decisional priority. Participants indicated genetic information was not extensively discussed or fully explained by providers.

Conclusions: Results demonstrate how genetic counselors can be more involved in the pre-selection process to discuss the utility and limitations of genetic information, as well as address psychosocial issues common to the oocyte recipient experience.

This paper offers a comprehensive review of the gestational surrogacy process in the US, as well as internationally, focusing on the legal and ethical challenges that gestational carriers, intended parents, fertility providers, and OB/GYNs may face. The objective of this review article is to serve as an overview and provide information on legal, cultural, and ethical aspects of the decisions to pursue gestational surrogacy both for intended parents and gestational carriers in the US and globally. By understanding the surrogacy landscape and the obstacles, the surrogacy agencies and other involved parties can improve the surrogacy process to better serve all parties involved.