Adding a ketogenic dietary intervention to IVF treatment in patients with polycystic ovary syndrome improves implantation and pregnancy.

Patients with polycystic ovary syndrome (PCOS) on a high-carbohydrate diet intrinsically suffer from exacerbated glucotoxicity, insulin resistance (IR), and infertility. Lowering the carbohydrate content has improved fertility in patients with IR and PCOS; however, the effects of a well-controlled ketogenic diet on IR and fertility in PCOS patients undergoing in vitro fertilization (IVF) have not been reported. Twelve PCOS patients with a previous failed IVF cycle and positive for IR (HOMA1-IR>1.96) were retrospectively evaluated. Patients followed a ketogenic diet (50 g of total carbohydrates/1800 calories/day). Ketosis was considered when urinary concentrations were > 40 mg/dL. Once ketosis was achieved, and IR diminished, patients underwent another IVF cycle. The nutritional intervention lasted for 14 ± 11 weeks. Carbohydrate consumption decreased from 208 ± 50.5 g/day to 41.71 ± 10.1 g/day, which resulted in significant weight loss (-7.9 ± 1.1 kg). Urine ketones appeared in most patients within 13.4 ± 8.1 days. In addition, there was a decrease in fasting glucose (-11.4 ± 3.5 mg/dl), triglycerides (-43.8 ± 11.6 mg/dl), fasting insulin (-11.6 ± 3.7 mIU/mL), and HOMA-IR (-3.28 ± 1.27). All patients underwent ovarian stimulation, and compared to the previous cycle, there was no difference in oocyte number, fertilization rate, and viable embryos produced. However, there was a significant improvement in the implantation (83.3 vs. 8.3 %), clinical pregnancy (66.7 vs. 0 %), and ongoing pregnancy/live birth rates (66.7 vs. 0 %). Here, restriction in carbohydrate consumption in PCOS patients induced ketosis, improved key metabolic parameters, and decreased IR. Even though this did not affect oocyte or embryo quality or quantity, the subsequent IVF cycle significantly improved embryo implantation and pregnancy rates.

Surgical and nutritional interventions for endometrial receptivity: A case report and review of literature.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disease that combines metabolic, reproductive, and psychological dysfunctions. Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertility. Insulin resistance (IR) is a pathological state of inadequate response to insulin that affects reproduction in PCOS, as damage caused by IR at the endometrial level becomes an obstacle for embryo implantation. Reversing IR resulted in spontaneous pregnancies in PCOS patients, indicating that metabolic corrections improve endometrial dysfunctions. Mesenchymal stem-cell treatment has also corrected endometrial quality and lead to pregnancies in patients with Asherman's syndrome. We propose a combination of nutritional intervention with the surgical placement of stem cells to improve endometrial quality to achieve pregnancy in a PCOS patient undergoing in vitro fertilization (IVF) treatment. CASE SUMMARY: After two failed IVF cycles, a metabolic intervention, consisting of a ketogenic diet with daily consumption of 50 g of carbohydrates (CH), was indicated until pregnancy. Metabolic Syndrome was assessed using the Harmonizing Definition (3 of 5 pathologies: Central obesity, hypertension, hyperglycemia, hypertriglyceridemia, and dyslipidemia), and the Homeostatic Model Assessment of IR (HOMA-IR) was used to measure the level of IR. Once IR improved, endometrial quality improved. However, two day 5-thawed embryos (euploid, donated oocyte-partner's sperm) failed to implant, suggesting endometrial quality improvement was insufficient. Therefore, transmyometrial implantation of mesenchymal stem cells from the stromal vascular fraction of adipose tissue was performed to enrich the endometrial stem cell niche. Minimal endometrial mean thickness for embryo transfer (6.9 mm) was achieved three months after stem cell treatment and continuous dietary control of IR. Two euploid-day 5-thawed embryos (donated oocyte-partner's sperm) were transferred, and embryo implantation was confirmed on day 14 by ß-hCG serum levels. Currently, a 37 wk baby girl is born. CONCLUSION: In PCOS, endometrial quality can be improved by combining nutrient-based metabolic correction with endometrial stem cell niche enrichment.

Successful management of cervical ectopic pregnancy with embryo reduction: report of three cases.

If methotrexate (MTX) fails to resolve cervical ectopic pregnancies (CEP), the remaining surgical options result in the potential loss of the patient's fertility. Therefore, we examined if the embryo reduction technique can resolve the CEP without any complications while conserving the patient's fertility. We report three cases in which CEP didn't respond to MTX but was successfully solved by embryo reduction. Each patient underwent a standard in vitro fertilization (IVF) protocol. Once CEP was confirmed, the pregnancy's location, the fetus's size and gestational sac and heartbeat were determined. Afterward, embryo reduction was performed under general anesthesia (operative time: ~30 min). All patients had successful procedures without any postoperative complications. Since the procedure, one woman was pregnant and delivered, the second has registered a positive ß-human chorionic gonadotropin test and the last is waiting for IVF preparation. In summary, embryo reduction is a feasible approach in the management of CEP with favorable fertility outcomes.

Initial ovarian sensitivity index predicts embryo quality and pregnancy potential in the first days of controlled ovarian stimulation.

BACKGROUND: To determine if a modified ovarian sensitivity index (MOSI), based on initial follicular measurements and the initial follicle-stimulating hormone (FSH) dose, can predict the production of high-quality embryos for successful implantation during in vitro fertilization (IVF). METHODS: This study consisted of two phases: 1) a retrospective study and 2) a prospective observational study. For the first phase, 363 patients charts were reviewed, of which 283 had embryos transferred. All women underwent a standardized antagonist-based IVF protocol. At the first follow-up (Day 3/4), the number and size of the follicles were determined. MOSI was calculated as ln (number follicles (≥6 mm) × 1000 / FSH initial dose). Afterward, the number and quality of the ova, embryo development, and the number and quality of the blastocysts were determined. Embryo implantation was confirmed by ß-hCG. For the second phase, 337 IVF cycles were followed to determine MOSI's accuracy. RESULTS: MOSI could predict the production of ≥4 high-quality embryos by Day 2 (AUC = 0.69, 95%CI:0.63-0.75), ≥2 blastocysts (AUC = 0.74, 95%CI:0.68-0.79), and ≥ 35% rate of blastocyst formation (AUC = 0.65, 95%CI:0.58-0.72). Using linear regression, MOSI was highly associated with the number of ova captured (ß = 5.15), MII oocytes (ß = 4.31), embryos produced (ß = 2.90), high-quality embryos (ß = 0.98), and the blastocyst formation rate (ß = 0.06, p < 0.01). Using logistic regression, MOSI was highly associated with achieving ≥4 high-quality embryos (odds ratio = 2.80, 95%CI:1.90-4.13), ≥2 blastocysts (odds ratio = 3.40, 95%CI:2.33-4.95), and ≥ 35% blastocysts formation rate (odds ratio = 1.96, 95%CI:1.31-2.92). This effect was independent of age, BMI, and antral follicle count. For implantation, MOSI was significantly associated with successful implantation (odds ratio = 1.79, 95%CI:1.25-2.57). For the prospective study, MOSI was highly accurate at predicting ≥6 high-quality embryos on Day 2 (accuracy = 68.5%), ≥6 blastocysts (accuracy = 68.0%), and a blastocyst formation rate of ≥35% (accuracy = 61.4%). CONCLUSION: MOSI was highly correlated with key IVF parameters that are associated with achieved pregnancy. Using this index with antagonist cycles, clinicians may opt to stop an IVF cycle, under the assumption that the cycle will fail to produce good blastocysts, preventing wasting the patient's resources and time.

Prediction of severe ovarian hyperstimulation syndrome in women undergoing in vitro fertilization using estradiol levels, collected ova, and number of follicles.

OBJECTIVE: Our objective was to determine whether estradiol (E2) levels (Day 3 and fold change to Day 10), antral follicle count (AFC), and number of ova collected could predict ovarian hyperstimulation syndrome (OHSS) and culdocentesis intervention. METHODS: We conducted a retrospective review of patient charts between January 2008 and December 2017. OHSS was defined using American Society for Reproductive Medicine criteria. Predictability was evaluated by measuring the area under the receiver operating characteristic curve (AUC). RESULTS: The cohort included 319 women (166 controls, 153 OHSS, of whom 54 had severe OHSS). The OHSS group had higher E2Day 3 (249 ± 177 vs. 150 ± 230 ng/L), E2FoldChange (32.2 ± 29.1 vs. 20.1 ± 23.8), AFC (18.2 ± 9.1 vs. 11.6 ± 8.3), and number of ova collected (21.1 ± 9.0 vs. 10.1 ± 6.5). E2Day 3 (AUC = 0.76, 95%CI: 0.71-0.82), E2FoldChange (AUC = 0.71, 95%CI: 0.65-0.77), AFC (AUC = 0.75, 95%CI: 0.70-0.81), and number of ova collected (AUC = 0.85, 95%CI: 0.81-0.89) were predictive for OHSS. All variables were predictive for culdocentesis intervention (E2Day 3: AUC = 0.63, 95%CI: 0.55-0.70; E2FoldChange: AUC = 0.63, 95%CI: 0.55-0.71; AFC: AUC = 0.74, 95%CI: 0.68-0.80; number of ova collected: AUC = 0.80, 95%CI: 0.75-0.85). CONCLUSIONS: Day 3 E2 levels and number of ova collected predict patients who could develop OHSS and may require culdocentesis.

Assessment of Prostaglandin-Endoperoxide Synthase 2 and Versican gene expression profile from the cumulus cells: association with better in vitro fertilization outcomes.

BACKGROUND: Current methods for determining superior embryo quality (morphological assessment) are unable to compensate for poor pregnancy outcomes. Due to the importance of the cumulus-oocyte complex and the value of cumulus cells (CCs) as markers of embryo health, we determined the association between the CCs gene expression of the Prostaglandin-Endoperoxide Synthase 2 (PTGS2) and Versican (VCAN) with pregnancy. METHODS: One hundred forty-nine women, suffering from infertility and undergoing IVF, were included in this study (age: 29-46 years; BMI = 25.5 ± 5.0 kg/m2). Patients underwent a standard IVF protocol. CCs were isolated during oocyte retrieval, and their RNA was isolated using Trizol. The mRNA expression of PTGS2, VCAN, and L19 was measured by qPCR. The PVL index, (PTGS2 + VCAN)*L19normalized, was determined for each oocyte. Clinical pregnancy was confirmed by ß-hCG and the presence of a fetal heartbeat. Associations were determined by ROC curves or logistic regression. RESULTS: There was no correlation between the PVL index and morphological scores. Using only single embryo transfers (SETs), we determined that the PVL index was associated with pregnancy (ß-hCG: AUC = 0.87, 95%CI: 0.74-1.00) with an optimal cutoff value of 58.2. Using the complete cohort (consisting of SETs, and patients with 2, 3, or 4 embryos transferred), the presence of at least one embryo with a PVL index score ≥ 58.2 was associated with a greater probability of achieving pregnancy (ß-hCG: odds ratio = 17.15, 95%CI: 6.82-43.18, p < 0.001). CONCLUSION: Transferring at least one embryo with a PVL index score ≥ 58.2, generates a higher chance of achieving pregnancy.

The role of LH in ovarian stimulation.

LH is a glycoprotein that plays a crucial role in folliculogenesis during the natural ovarian cycles. It has the same activity and shares receptors with hCG. However the use of LH in combination with FSH in controlled ovarian stimulation remains controversial. A practical approach concerning the usefulness of LH according to the endogenous level of LH is described herein. Specific groups of patients can benefit from ovarian stimulation with LH. New applications of LH/hCG activity are also discussed.