This cohort study is aimed to determine if higher number of oocytes retrieved affects the rate of euploidy in the embryos of women undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A). A negative trend between the number of oocytes retrieved and embryo euploidy rate was observed using Visual Analytics software, especially when a higher number of oocytes were retrieved. After regression analysis, patient age was the only variable found to have a statistically significant negative effect ( p < 0.0001) on euploidy rate in all regression models. Number of oocytes retrieved was not found to have a statistically significant effect on euploidy rate when analyzed per number of biopsied blastocysts ( p = 0.5356), per number of oocytes retrieved ( p = 0.1025), and per number of fertilized oocytes ( p = 0.7241). The parameter estimates in the linear regression models were negative for number of oocytes retrieved. This study shows a statistically significant effect between patient age and embryo euploidy rate, which is already known. There is some evidence to suggest that higher number of oocytes retrieved may negatively impact the number of euploid embryos per number of oocytes retrieved based on the visual analytic graphs, p value approaching significance, and the negative parameter estimates in the regression models.
Cumulus cell (CC) clumps that associate with oocytes provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function, and CC metabolism may be predictive of oocyte competence for in vitro fertilization. CCs are thought to be highly glycolytic, but data on the use of other potential carbon substrates are lacking in humans. This prospective and blinded cohort study was designed to examine the substrate utilization of CCs by age and oocyte competence. Individual sets of CC clumps from participants were removed after oocyte retrieval procedure then, incubated with stable isotope labeled substrates, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA. The acyl-chain of acetyl-CoA contains 2 carbons that can be derived from C-13-labeled substrates resulting in an M + 2 isotopologue that contains 2 C-13 atoms. Comparing the fate of three major carbon sources, mean enrichment of M + 2 acetyl-CoA (mean, standard deviation) was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Due to this unexpected high and variable labeling from acetate, we then examined acetyl-CoA mean % enrichment from acetate in 278 CCs from 21 women <= 34 (49.06, 12.73) decreased with age compared to 124 CCs from 10 women >34 (43.48, 16.20) (p = 0.0004, t-test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M + 2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: -6.02, CI: -1.74,-13.79, p = 0.013). Acetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of non-glucose substrates should be investigated relative to oocyte function and age-related fertility.
Various separation techniques are utilized to select the best sperm for intrauterine insemination and intracytoplasmic sperm injection. Sperm selected using SSD have been reported to have less DNA fragmentation, which may optimize fertility outcomes, but there is limited information on its effects on other sperm parameters. The objective of this study was to compare the SSD to SSU on sperm morphology and motility parameters objectively measured by a computer assisted sperm analyzer (CASA). Semen samples from 25 patients were assigned an accession number and de-identified. All semen specimens were randomly split between the two sperm separation methods. Liquefied semen (850 μL) was placed into the inlet port of the ZyMōtTM SSD and the same volume was placed into a 15 ml centrifuge tube for SSU. Sperm washing medium (750 μL) was layered over the SSD membrane, and the same volume was layered on top of the semen specimen within the centrifuge tube for SSU. Both were incubated at 37 °C for 30 minutes. The sperm suspension (500 μL) was then drawn from the outlet port of the SSD, and 500 μL was removed from the top of the upper layer in the SSU tube. Two subsamples (6 μL each) from each treatment were analyzed using a Hamilton Thorne CEROS II CASA. Mean sperm parameters recorded included concentration, % motility, % progressive motility, path velocity (VAP), progressive velocity (VSL), track speed (VCL), lateral head amplitude (ALH), beat cross frequency (BCF), straightness (STR), linearity (LIN), elongation % and area. Normal morphology was read blindly by one senior andrology technologist and recorded. The data was analyzed via Statistical Analysis System utilizing a matched pairs t-test comparing SSD to SSU. Significance was defined as p<0.05. Two sperm parameters were higher after SSD separation compared to SSU including concentration (21.2 vs 16.99 M/mL; p= 0.0023) and mean ALH (4.16 vs 3.99 μm; p=0.0081). However, several more motility parameters were higher after SSU compared to SSD including VAP (90.07 vs 92.24 μm/s; p=0.0410), VSL (82.69 vs 85.22 μm/s; p=0.0250), BCF (29.42 vs 31.05 Hz; p=0.0001), STR (90.4 vs 91.16 %; p=0.0271) and LIN (68.48 vs 70.28%; p=0.0055.) There was no significant difference seen in % normal morphology. In our study, SSD prepared sperm resulted in a higher concentration of sperm while SSU prepared sperm resulted in higher motility parameters. Therefore, different sperm quality parameters may be optimized by different sperm separation techniques.
Background. While growth hormone (GH) is commonly used as an adjuvant treatment to controlled ovarian stimulation (COS) for in vitro fertilization (IVF) cycles, the data regarding its efficacy is inconsistent. Design. A retrospective matched cohort study of poor responder patients who underwent COS without the use of GH (COS-GH) subsequently followed by COS cycles that included adjuvant GH (COS+GH) treatment. Materials and Methods. A list of all patients having filled a prescription for GH from January 2018 – March 2020 was obtained. GH was administered daily at 3mg (9IU) starting on the first day of stimulation and ending on the day of trigger. Only women who had documentation of a previous cycle without the use of GH were included in the study. Results. 182 cycles (91 patients) were included in the study, and COS-GH cycles were compared to COS+GH cycles. The total dose of gonadotropins used (5757 vs 4252 mIU, p=0.002), duration of stimulation (10.4 vs 10.1 days, p=-.045), maximum Estradiol (E2) (2411 vs 1932 pg/ml, p=0.010), endometrial thickness (11.2 vs 10.6 mm, p=0.010), number of oocytes retrieved (14.2 vs 11.8, p=0.001), number of mature oocytes (11.1 vs 9.7, p=0.028), number of blastocysts (3.98 vs 2.56, p=<0.001) and number of usable blastocysts (2.5 vs 1.6, p=<0.001) were all significantly greater in the GH group. Conclusions. Adding GH to the COS protocol in poor responder patients may lead to improvements in the number of oocytes retrieved, number of mature oocytes, endometrial thickness, number of blastocysts, the number of usable blastocysts.
While growth hormone (GH) is commonly used as an adjuvant treatment to controlled ovarian stimulation (COS) for IVF cycles, the data regarding its efficacy is inconsistent. A retrospective matched cohort study of poor responder patients who underwent COS without the use of GH (COS-GH) subsequently followed by COS cycles that included adjuvant GH (COS+GH) treatment. A list of all patients having filled a prescription for GH from January 2018 – March 2020 who were undergoing IVF with a single provider was obtained. GH was administered daily at 3mg (9IU) starting on the first day of stimulation and ending on the day of trigger. Only women who had documentation of a previous cycle without the use of GH were included in the study. Several different outcomes were compared including total dose of gonadotropins used, duration of stimulation, number of follicles, number of mature oocytes, endometrial thickness, maximum estradiol (max E2) level, maximum progesterone (max P4) level, number of oocytes retrieved, number of mature oocytes, number of blastocyst embryos (blasts), number of usable blasts and percentage of usable blasts. Usable blasts were defined as those embryos that were transferred to the uterus or frozen. Paired t-tests were used by an independent statistician to analyze the data, and statistical significance was set at p<0.05. 182 cycles (91 patients) were included in the study, and COS-GH cycles were compared to COS+GH cycles. The total dose of gonadotropins used (4252 vs 5757 mIU, p=0.002), duration of stimulation (10.1 vs 10.4 days, p=-.045), max E2 (1932 vs 2411 pg/ml, p=0.010), endometrial thickness (10.6 vs 11.2 mm, p=0.010), number of oocytes retrieved (11.8 vs 14.2, p=0.001), number of mature oocytes (9.7 vs 11.1, p=0.028), number of blasts (2.56 vs 3.98, p=<0.001) and number of usable blasts (1.6 vs 2.5, p=<0.001) were all significantly greater in the GH group. Adding growth hormone to the COS protocol in poor responder patients may lead to improvements in the number of oocytes retrieved, mature oocytes, endometrial thickness, number of blastocysts, and the number of usable blastocysts.
