Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Feasibility of in vitro maturation of oocytes collected from patients with malignant ovarian tumors undergoing fertility preservation.

OBJECTIVE: In vitro maturation of oocytes collected from oophorectomy samples might be a promising approach in the field of oncofertility. In this study, we evaluate the feasibility of in vitro maturation of oocytes collected from oophorectomy samples in patients with ovarian tumors. METHODS: This prospective observational study included 27 patients with malignant ovarian tumors. Patients underwent oophorectomy and ovarian tissue was examined for the presence of immature cumulus-oocyte complexes. These were matured in vitro for 48 hours. Mature oocytes were vitrified or used for fertilization. Serum anti-müllerian hormone (AMH) levels were analyzed in 11 patients and cancer antigen 125 (CA125) levels in 16 patients. RESULTS: In this study, 99 cumulus-oocyte complexes were obtained from 17 patients (63%). The mean (SE) age of the patients was 33.47±1.86 years (range 16-44). A total of 14 patients had ovarian cancer (IA-IVB), one patient had ovarian cancer IC and endometrial cancer IA, one patient had endometrial cancer stage IA with metastasis into the ovary, and one patient had cervical cancer stage IIB with metastasis in the ovary. Oocytes were not obtained in 10 patients who had diminished ovarian reserve due to age (>38 years), chemotherapy, or previous surgical treatment. On average, 5.8 cumulus-oocyte complexes were obtained per patient. The maturation rate was 40.4% with an average of 2.8 metaphase II oocytes per patient. As a result of the study, 3 blastocysts in 3 patients and 22 oocytes in 9 patients were vitrified. CONCLUSIONS: In vitro maturation of oocytes collected from oophorectomy samples in patients with malignant ovarian tumors may result in oocyte and blastocyst vitrification. However, it should be offered to patients before surgery and chemotherapy. This method might be most beneficial in patients younger than 38 years, with AMH serum levels >1 ng/mL and without a large tumor burden.

Improved maturation competence of ovarian tissue oocytes using a biphasic in vitro maturation system for patients with gynecological malignancy: a study on sibling oocytes.

PURPOSE: To investigate the developmental competence of ovarian tissue oocytes from patients with gynecological tumors using a biphasic in vitro maturation system with capacitation (CAPA-IVM) in comparison with standard IVM. METHODS: This sibling pilot study included 210 oocytes in 10 patients with gynecological malignancies. After ovariectomies, ovaries were cut into even halves and immature cumulus-oocyte complexes (COCs) were retrieved from the ovarian tissue. COCs were separately cultured in either a biphasic CAPA-IVM system for 53 h or in standard IVM for 48 h. After IVM, all COCs were denuded and mature oocytes were either vitrified (N=5) or used for ICSI (N=5). Embryos were cultured for 5-6 days and obtained blastocysts were vitrified. RESULTS: Use of the CAPA-IVM system led to a higher meiotic maturation rate in ovarian tissue oocytes (OTO) compared to standard IVM (56 vs 35%, p=0.0045) and had a tendency to result in lower degeneration after IVM. Only the CAPA-IVM method supported blastocyst formation. CONCLUSIONS: The biphasic in vitro maturation system improved the competence of OTO in comparison to the standard IVM method. The study suggests that fertility preservation programs could become more efficient using IVM after capacitation culture.

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

PROBLEM: Interleukin 8 (IL-8), vascular endothelial growth factor A (VEGFA), its receptors 1 (VEGFR1) and 2 (VEGFR2) are associated with ovarian hyperstimulation syndrome (OHSS) pathophysiological mechanisms. The aim of this study was to evaluate the concentrations of these cytokines depending on the way of ovulation triggering. METHOD OF STUDY: A total of 51 high-responder patients underwent IVF program and received gonadotropin-releasing hormone agonists (GnRHa) trigger + 1500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day (group I), dual trigger (GnRHa + 1500 IU hCG; group II), or hCG trigger 10,000 IU (group III) for the final oocyte maturation. The concentrations of cytokines were evaluated in serum by the enzyme-linked immunosorbent assay kit. RESULT(S): VEGFR2 levels were significantly lower in groups I and II than in group III in serum on the OPU (I vs. III, p = .0456; II vs. III, p = .0122) and OPU + 5 day (I vs. III, p = .0004; II vs. III, p = .0082). VEGFA levels were lower in group I than in group III (p = .0298) on the OPU day, however, were similar in all groups on the OPU + 5 day. CONCLUSION(S): A small dose of hCG elicits similar concentrations of VEGFA to a full dose of hCG; however, GnRHa triggering reduces the concentrations of VEGFR2, which could lead to the OHSS prevention.

Bioethical and Legal Issues in 3D Bioprinting.

Bioethical and legal issues of three-dimensional (3D) bioprinting as the emerging field of biotechnology have not yet been widely discussed among bioethicists around the world, including Russia. The scope of 3D bioprinting includes not only the issues of the advanced technologies of human tissues and organs printing but also raises a whole layer of interdisciplinary problems of modern science, technology, bioethics, and philosophy. This article addresses the ethical and legal issues of bioprinting of artificial human organs.

Cumulus cell gene expression in luteal-phase-derived oocytes after double stimulation in one menstrual cycle.

RESEARCH QUESTION: Does double stimulation (DuoStim) affect cumulus cell gene expression in luteal-phase-derived oocytes? DESIGN: This prospective observational study included 39 patients with reduced ovarian reserve. Fifteen patients (group 1) underwent IVF with a gonadotrophin-releasing hormone antagonist in the follicular phase and 24 patients (group 2) underwent DuoStim. A total of 149 cumulus cell samples were divided into two groups according to the phase of the cycle: group 1 included 55 follicular-phase-derived oocytes and group 2 included 94 luteal-phase-derived oocytes. The expression levels of the following genes were assessed using quantitative polymerase chain reaction: HAS2, VCAN, ALCAM, PTGS2, GREM1, ITPKA, TRPM7, SDC4, CALM2, SPSB2, TP53I3, PGR and PFKP. RESULTS: The expression of 10 out of 13 genes in cumulus cells was similar between DuoStim luteal-phase-derived oocytes and follicular-phase-derived oocytes. A significant increase in the mRNA levels of VCAN (15.542 ± 6.8 versus 20.353 ± 10.58; P = 0.001), SDC4 (1.016 ± 0.65 versus 1.318 ± 0.97; P = 0.013), and TP53I3 (0.185 ± 0.09 versus 0.270 ± 0.11; P = 1.19E-05) was observed in group 2. The number of oocytes collected (5.57 ± 2.3 versus 5.7 ± 2.7; P > 0.05) and the number of blastocysts were comparable between the groups (2.1 ± 2.1 versus 2.7 ± 2.2; P > 0.05). CONCLUSIONS: The DuoStim approach leads to changes in the follicular environment. It affects the expression levels of VCAN, SDC4, and TP53I3 in the cumulus cells of luteal-phase-derived oocytes. These results, however, did not correlate with oocyte maturation, embryo quality and pregnancy rate.

Cryopreservation of euploid blastocysts obtained after fertilization of in vitro matured ovarian tissue oocytes: a case report.

With the increased rate of stable remission after gonadotoxic cancer treatment, new methods of fertility preservation are required in order to provide the best possible care for oncological patients. Here, we report an original case of euploid blastocyst cryopreservation after in vitro maturation of ovarian tissue oocytes (OTO IVM). Thirty-three oocytes were obtained from the ovarian tissue after ovariectomy in the breast cancer patient. Six out of 12 matured oocytes fertilized successfully and 3 blastocysts were formed. Genetic investigation for mutations associated with this type of malignancy found that the patient is not a carrier. Preimplantation genetic testing was performed only for aneuploidies and found all 3 blastocysts to be euploid and suitable for embryo transfer. Our study showed that the ovarian tissue oocytes matured in vitro have the potential for euploid blastocyst formation after ICSI which could be screened for aneuploidies and inherited mutations and then be vitrified in order to provide the best fertility preservation strategy for women with cancer.

Should we transfer poor quality embryos?

BACKGROUND: To evaluate if it is safe and effective to transfer poor quality embryos. METHODS: It was a retrospective analysis using individual patient data with positive controls. All patients undergoing embryo transfers of poor quality embryos on day 3 or on day 5 as part of fresh In Vitro Fertilization (IVF) cycles performed between 2012 and 2016. This study assessed a total of 738 poor quality embryos from 488 IVF programs. 261 embryo transfers were performed on day 3 (402 embryos were transferred) and 227 on day 5 (336 embryos were transferred). Control group consisted of 9893 fair and good quality embryos from 5994 IVF programs. Outcome rates were compared with two-tailed Fisher exact test using fisher.test function in R software. 95% confidence intervals for proportions were calculated using the Clopper-Pearson method with binom.test function in R. The groups of patients with poor vs. good and fair quality embryos were compared by age, body mass index(BMI), number of oocytes, female and male main diagnosis, cycle type, controlled ovarian stimulation (COS) protocol, the starting day of gonadotropin administration, the starting dose of gonadotropins, the total dose of gonadotropins, the total number of days of gonadotropins administration, the starting day of gonadotropin-releasing hormone (GnRH) agonist administration, the total number of ampoules of GnRH-agonist used, day of the trigger of ovulation administration and the type of the trigger of ovulation using the Student's t-test for interval variables and with the chi-square test for nominal variables. RESULTS: No significant differences in the implantation rate, clinical pregnancy rate, miscarriage rate, live births, and the number of children born were found between the groups of poor quality embryos transferred on day 3 and day 5. Though the implantation rate was lower for the group of poor quality embryos, than for the control (13.9% vs 37.2%), statistically significant differences between the proportion of implanted embryos which resulted in clinical pregnancies and live births in both groups were not observed (72% vs 78.2 and 55.8% vs 62.0% respectively). CONCLUSION: Transfer of poor quality embryos at either day 3 or day 5 have a low potential for implantation, though those embryos which successfully implanted have the same potential for live birth as the embryos of fair and good quality. This study supports that it is safe to transfer poor quality embryos when they are the only option for fresh embryo transfer (ET).