Associations among morphological parameters, clinical factors and euploid blastocyst formation.

OBJECTIVE: To evaluate the association among embryonic morphological parameters, clinical factors and euploid blastocyst formation. METHODS: This prospective cohort study included 422 blastocysts from 135 patients who had undergone preimplantation genetic analysis after intracytoplasmic sperm injection (ICSI). RESULTS: Of 422 blastocysts, 200 (47.4%) were euploid and 222 (52.6%) aneuploid. Women aged older than 38 years were more likely to develop aneuploid embryos (OR: 3.4, CI: 2.2-5.4, p<0.001). Poor ovarian reserve (OR: 3.3, p<0.001), increased male age (39.0 versus 40.7, p=0.019), and decrease in sperm percentage with normal morphology (2.5% vs. 1.9%, p=0.047) were associated with aneuploidy. Type C trophectoderm (TE) and type C inner cell mass were associated with a high risk of embryo aneuploidy, with OR of 4.1 (CI: 2.2-7.7, p<0.001) and 1.7 (CI: 1.01-3.0, p=0.048), respectively. Logistic regression analysis revealed maternal age and type C TE as the main risk factors for aneuploidy. Among combinations of factors, the best marker for the risk of aneuploidy was maternal age older than 38 years, combined with a type-C embryo with trophectoderm, which showed a positive predictive value of 88.6% and a specificity of 97.5%. CONCLUSIONS: Trophectoderm and type-C inner cell mass are the main embryo risk factors for aneuploidy, explaining approximately 71% and 60% of the risk, respectively. Among clinical factors, advanced maternal and paternal age (older than 38 and 36 years, respectively), antral follicles (<5), and a low percentage of sperm with normal morphology increased the risk of embryonic aneuploidy.

Association of FSHR, LH, LHR, BMP15, GDF9, AMH, and AMHR polymorphisms with poor ovarian response in patients undergoing in vitro fertilization.

OBJECTIVE: This paper aimed to assess the correlation between LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15 polymorphisms, which are related to follicular development, and decreased ovarian response in women undergoing controlled ovarian hyperstimulation (COH) for IVF. METHODS: This age-matched case-control study included three or four controls per woman undergoing COH. Controls were women with normal ovarian response (NOR) and cases were women with poor ovarian response (POR) in oocyte retrieval (three or fewer oocytes). DNA was extracted from peripheral blood and potential associations with gene polymorphisms related to follicular development (LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15) were analyzed. RESULTS: Sixty-six patients were included, 52 in the NOR and 14 in the POR group. Two GDF9 polymorphisms were associated with follicular response after COH, one associated with POR - the presence of a mutant polymorphism in heterozygosis and homozygosis of the GDF9 398-39 (C to G) [23% NOR versus 68% POR (OR 4.01, CI 1.52-10.6, p=0.005)] - and another associated with protective response - the presence of normal homozygosis of GDF9 (C447T) [19.2% NOR versus 50% POR (OR 0.34, IC 0.14-0.84, p=0.019)]. No additional associations were found between the other analyzed polymorphisms and POR. CONCLUSIONS: This study found that GDF9 appears to play an important role in follicular development, whereas polymorphisms in its DNA chain may negatively affect ovarian reserve, such as 398-39 (C to G), or positively, as seen in C447T.

The usefulness of metaphase I oocytes in women who undergo controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

OBJECTIVE: The aim of this study was to evaluate the fertilization and blastocyst formation rates of oocytes in metaphase I (MI) obtained from women who underwent controlled ovarian hyperstimulation (COH) for intracytoplasmic injection. METHODS: A prospective cohort study that included women from whom at least 1 MI and 1 MII oocyte were obtained after COH was performed. We collected 1,907 oocytes from 164 women (1291 MII, 352 MI and 258 prophase I or atretic). After oocyte classification, the MII and MI oocytes were incubated for 4 hours. RESULTS: After 4 hours, the rescue maturation rate was 57.2%; 205 MI oocytes matured to MII oocytes in vitro (rescued MI-MII group), and 153 remained in MI (arrested MI group). The normal fertilization rates were directly associated with oocyte maturation, with rates of 79.1%, 60.2%, and 31.9% in MII, MI-MII and MI oocytes, respectively (p<0.001). Group arrested MI had an odds ratio (OR) of 7.6 (CI 5.2 - 11.2, p<0.001) for abnormal fertilization compared with Group MII. The blastocyst formation rate was directly associated with oocyte maturation, at 36.4% for MII, 11.4% for MI-MII and 0.6% for MI. CONCLUSION: Oocytes collected at the MI stage after OCH that did not mature to MII after rescue maturation had a blastocyst formation rate of only 0.6%, while those in MII and MI-MII had rates of 36.4% and 11.4%, respectively. However, we found a pregnancy with the birth of a healthy baby from a blastocyst formed after intracytoplasmic sperm injection (ICSI) of an MI oocyte.

GDF9 polymorphisms: influence on ovarian response in women undergoing controlled ovarian hyperstimulation.

OBJECTIVE: The study looked into the possible influence of GDF9 polymorphisms on ovarian response in women with a normal ovarian reserve undergoing controlled ovarian hyperstimulation for in vitro fertilization (IVF). METHODS: This cross-sectional study included 67 women with normal ovarian reserve aged 30-39 years submitted to controlled ovarian hyperstimulation for IVF. We sequenced four polymorphisms in the GDF9 gene (C398G, C447T, G546A, and G646A) and analyzed their influence on follicular and oocyte outcomes. RESULTS: The mutant allele C398G decreased the total number of follicles >17mm (6.49 vs. 4.33, p=0.001), total number of follicles (10.11 vs. 7.33, p=0.032), number of MII oocytes retrieved, and serum progesterone levels on trigger day. The C447T polymorphism was associated with a greater number of follicles between 12 and 14 mm on the day of r-hCG, while the G546A polymorphism was associated with lower serum progesterone levels on trigger day. CONCLUSIONS: GDF9 gene polymorphisms C398G and C447T adversely affected ovarian response in women undergoing controlled ovarian hyperstimulation. These findings show that in addition to playing a role in the early stages of folliculogenesis, GDF9 polymorphisms have an important impact on the final stage of oocyte development.

Causes of recurrent miscarriage after spontaneous pregnancy and after in vitro fertilization.

PROBLEM: We aimed to investigate the main causes of recurrent miscarriage (RM) in patients with losses after spontaneous gestation (SG) and after in vitro fertilization (IVF). METHOD OF STUDY: A prospective case-control study was conducted. The eligible patients were women who had experienced two or more consecutive abortions after <12 weeks' gestation, two consecutive losses after SG, or two consecutive losses after IVF. All patients were subjected to the following evaluations: karyotyping of the aborted material, alloimmune and autoimmune marker testing, and acquired and hereditary thrombophilia marker testing. RESULTS: In total, 58 patients were eligible: 32 patients with RM after SG and 26 patients with RM after IVF. The factors associated with RM were genetic (29%), immune (14%), thrombophilic (21%), and thrombophilic and immune (24%), and only 12% of the cases were idiopathic. Comparing the two study groups (SG and IVF), all studied factors were similar, except for a higher ANA positivity observed in the SG group (SG 30.4% vs IVF 5.3%, OR 8.6 (CI 1.1-21.1, P .048). CONCLUSION: Our study identified the possibly factors associated with recurrent miscarriage in 86% of the cases, and these factors appear to be similar in patients with recurrent miscarriage after spontaneous gestation and IVF. This study demonstrates that IVF with PGT-A with euploid embryo transfer could reduce abortions by up to 29%, but other factors need to be investigated even in patients undergoing in vitro fertilization.