Whole-Ovary Laparoscopic Incisions Improve Hormonal Response and Fertility in Patients with Extremely Poor Ovarian Response.

STUDY OBJECTIVE: Recent findings have shown mechanical fragmentation of ovarian cortex and ovarian drilling could promote follicle growth in patients with premature ovarian insufficiency and polycystic ovarian syndrome, respectively. A common element shared by these treatments is the mechanical disturbance of ovarian extracellular matrix tissues. We thus hypothesized a simplified whole-ovary laparoscopic incision (WOLI) procedure may provide the intrinsic stimuli needed to activate resting follicles in patients with an extremely poor ovarian response (EPOR) who had negligible chance of becoming pregnant with their own oocytes via modern in vitro fertilization practice. DESIGN: Retrospective pilot study. SETTING: The study was conducted in a research medical center in Taiwan. PATIENTS: Women who had multiple canceled ovarian stimulation cycles due to the lack of follicle growth were recruited. A total of 6 patients with EPOR received the WOLI procedure, which covers the whole surface of ovaries, in 2015 to 2017. INTERVENTIONS: After receiving an outpatient WOLI procedure, ovarian response and follicle growth were monitored for 90 days with or without gonadotropin stimulation. Embryo quality and clinical outcomes were analyzed. MEASUREMENTS AND MAIN RESULTS: After the WOLI treatment, 5 of 6 patients had significant increases in serum estradiol level and improved follicle growth (p = .001). Multiple oocytes were retrieved from each of these patients, and it led to thawed embryo transfer (ET) cycles in 4 patients (p = .010). On average, the duration from the WOLI procedure to the first ovum pickup was 24 days (11 to 58 days). After ET, 2 patients became pregnant and delivered healthy babies. Two other patients received ET, and 1 led to a chemical pregnancy. One patient had cryopreserved embryos with pending transfer. CONCLUSION: The standardizable WOLI procedure restored hormonal responses in a majority of patients with EPOR. Further validation of this novel and yet simple laparoscopic procedure, which requires only 1 laparoscopic surgery, may provide a practical option to reactivate the aging ovarian environment in patients with EPOR and premature ovarian insufficiency.

Obstetric and perinatal outcomes of pregnancy in patients with repeated implantation failure.

OBJECTIVE: Despite the great advance of assisted reproductive technology (ART) in recent decades, many IVF patients failed to achieve a pregnancy even after multiple IVF-ET attempts. These patients are considered to have repeated implantation failure (RIF). While exhausting efforts have been devoted to the improvement of pregnancy rate in RIF patients, it is not clear whether RIF patients have aberrant obstetric or perinatal outcomes after they eventually achieved a pregnancy. MATERIALS AND METHODS: Taking advantage of a relatively large database of IVF-ET cycles at the Chang Gung Memorial Hospital, we compared obstetric and perinatal outcomes of RIF patients who have a successful pregnancy after IVF-ET treatment(s) to those of control IVF-ET patients. RESULTS: Because multiple pregnancies are associated with a high risk of obstetric complications, we restricted the analysis to patients who had singleton pregnancies. Analysis of a total of 596 control and 46 RIF cases showed the rates of almost all obstetric and perinatal outcomes investigated are not different between the two groups. However, the rate of placental abruption in the RIF group (4.35%) appeared to be significantly higher than that of controls (0.50%; OR = 8.99). This difference is still statistically significant after adjustment with the age (adjusted OR = 8.2). CONCLUSION: While the rates of a spectrum of obstetric and perinatal outcomes are normal in RIF patients, these patients could have an enhanced risk of placental abruption. However, investigations with a large sample size are needed to substantiate this inference.

The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, oligo- or anovulation, and/or polycystic ovary. It frequently presents with dyslipidemia and insulin resistance. Recent studies have shown that the white adipose tissue-derived asprosin is elevated in humans with insulin resistance. Because many PCOS patients have a propensity to develop dyslipidemia and/or insulin resistance, asprosin metabolism could be dysregulated in PCOS patients. Accordingly, we investigated serum levels of asprosin, irisin, GIP, androgens, LH, glucose, insulin, and lipids as well as HOMA-IR, QUICKI and ISI Matsuda in a cohort of 444 PCOS patients and 156 controls. Patients were stratified based on metabolic syndrome risk factors (ATPIII [+] and [-] groups), or BMI (overweight and lean groups). The irisin level was significantly correlated with body weight, SBP, DBP, Ferriman-Gallwey score, and levels of TSH, triglycerides, glucose and insulin in the overall population, and was elevated in ATPIII(+) and overweight PCOS patients compared to corresponding controls. By contrast, asprosin levels in PCOS, ATPIII(+), or overweight patients were similar to those of corresponding controls. This finding indicated that the regulation of irisin, but not asprosin, metabolism is abnormal in PCOS patients, and this metabolic characteristic is distinctly different from that of diabetes patients.

Transcutaneous electrical acupoint stimulation (TEAS) treatment improves pregnancy rate and implantation rate in patients with implantation failure.

OBJECTIVE: Although major advances have greatly improved the outcomes of assisted reproductive technology in the last two cascades, there remains significant difficulty in achieving pregnancy for many patients even after repeated attempts of IVF. Interestingly, recent studies have shown that transcutaneous electrical acupoint stimulation (TEAS) can improve the reproductive outcomes of select IVF patients. To determine the utility of TEAS in improving IVF outcomes in patients with a history of implantation failure, we conducted a retrospective study of clinical outcomes of women, who had a prior history of unsuccessful pregnancy outcome after IVF-embryo transfer (IVF-ET), following TEAS treatment. MATERIALS AND METHODS: A total of 25 patients, who had failed to conceive after multiple IVF cycles in which good embryos were transferred, received noninvasive low frequency TEAS treatment prior to and during an IVF-ET cycle. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and implantation rate, were compared to those of prior cycles which received only standard IVF treatment. RESULTS: Analysis of reproductive outcomes showed that implantation rate and clinical pregnancy rate increased significantly in IVF cycles that included the TEAS treatment when compared to prior cycles that received only the standard IVF treatment in this cohort of patients. CONCLUSIONS: This surprising finding indicated that TEAS treatment is a promising technique to improve reproductive outcomes in difficult cases of IVF-ET. Because TEAS treatment is noninvasive and has high reproducibility, and can be applied with limited training, further refinement of this procedure would not only substantiate the beneficial effects of TEAS, but also allow the technique to be more effective and reproducible.

Detection of SEA-type α-thalassemia in embryo biopsies by digital PCR.

OBJECTIVE: Accurate and efficient pre-implantation genetic diagnosis (PGD) based on the analysis of single or oligo-cells is needed for timely identification of embryos that are affected by deleterious genetic traits in in vitro fertilization (IVF) clinics. Polymerase chain reaction (PCR) is the backbone of modern genetic diagnoses, and a spectrum of PCR-based techniques have been used to detect various thalassemia mutations in prenatal diagnosis (PND) and PGD. Among thalassemias, SEA-type α-thalassemia is the most common variety found in Asia, and can lead to Bart's hydrops fetalis and serious maternal complications. MATERIALS AND METHODS: To formulate an efficient digital PCR for clinical diagnosis of SEA-type α-thalassemia in cultured embryos, we conducted a pilot study to detect the α-globin and SEA-type deletion alleles in blastomere biopsies with a highly sensitive microfluidics-based digital PCR method. Genomic DNA from embryo biopsy samples were extracted, and crude DNA extracts were first amplified by a conventional PCR procedure followed by a nested PCR reaction with primers and probes that are designed for digital PCR amplification. RESULTS: Analysis of microfluidics-based PCR reactions showed that robust signals for normal α-globin and SEA-type deletion alleles, together with an internal control gene, can be routinely generated using crude embryo biopsies after a 106-fold dilution of primary PCR products. CONCLUSION: The SEA-type deletion in cultured embryos can be sensitively diagnosed with the digital PCR procedure in clinics. The adoption of this robust PGD method could prevent the implantation of IVF embryos that are destined to develop Bart's hydrops fetalis in a timely manner. The results also help inform future development of a standard digital PCR procedure for cost-effective PGD of α-thalassemia in a standard IVF clinic.