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.

Personalized regenerative strategies and molecular diagnosis for in vitro fertilization success: a case report.

Limited options are available for infertility associated with damaged or suboptimal tissues, typically the endometrium or ovaries. The goal of regenerative medicine is to restore function to specific tissues. Here, a 35-year-old female patient underwent two interventions of regenerative medicine: (i) autologous mesenchymal stem cells (MSCs) were applied in the myometrium, and (ii) intraovarian infusion of platelet-rich plasma (PRP). After two failed in vitro fertilization cycles (IVF), in which the endometrium was <5 mm, MSCs were applied, achieving a 7 mm trilaminar lining; however, the embryo quality remained poor. Therefore, intraovarian PRP was utilized for the next IVF cycle; the patient's response improved, and a euploid embryo developed. After the embryo transfer and a normal 38 weeks of pregnancy, a baby girl was born. Here, we demonstrate two forms of regenerative medicine that can be utilized to improve IVF.

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.

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.