The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed in vitro fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.

OBJECTIVE: Although previous research has suggested that risk for reoperation among hysteroscopic sterilization (HS) patients is more than ten times higher than for patients undergoing standard laparoscopic tubal ligation, little has been reported about these subsequent procedures. METHODS: This descriptive cohort study used a confidential online questionnaire to gather data from women (n=3,803) who volunteered information on HS followed by device removal surgery performed due to new symptoms developing after Essure placement. RESULTS: In this sample, mean age was 35.6 years and women undergoing hysterectomy after HS comprised 64.9% (n=2,468). Median interval between HS and hysterectomy was 3.7 (interquartile range, 3.9) years and mean age at hysterectomy was 36.3 years. Some patients (n=1,035) sought removal of HS devices and fallopian tubes only, while other miscellaneous gynecological procedures were also occasionally performed for Essure-associated symptoms. When data from all patients who had any post-Essure surgery besides hysterectomy were aggregated (e.g., device removal +“other” cases, n=1,335) and compared to those cases undergoing hysterectomy, mean age was significantly lower than for the hysterectomy group (34.4 vs. 36.3 years, respectively; P<0.01); uterus-conserving surgeries were also typically performed significantly earlier than hysterectomy (P<0.01). CONCLUSION: This investigation is the first to characterize specific gynecological operations after Essure, and suggests that the predominant surgical answer to HS complaints is hysterectomy for many women. Dissatisfaction with HS may represent an important indication for hysterectomy and additional study is needed to quantify this phenomenon.
Cohort Studies ; Contraception ; Device Removal ; Fallopian Tubes ; Female ; Humans ; Hysterectomy ; Reoperation ; Sterilization* ; Sterilization, Tubal

As clinicians and patients await consensus on intraovarian platelet-rich plasma (PRP) treatment, this project evaluated contemporary research trends in the literature. Methods: A PubMed/NLM search aggregated all ovarian PRP-related publications (n=54) to evaluate their scope, abstract utility, submission-to-publication interval, journal selected, article processing charge (APC), free reader access to full-text manuscripts, number and nationality of authors, and inclusion of international collaborators. The NIH Clinical Trials database was also audited. Results: Published output on intraovarian PRP has increased consistently since 2016, especially among investigators in Greece, Iran, USA, and Turkey. Between 2013 and 2021, 42 articles met the relevancy criteria, of which 40.5% reported clinical studies, small series, or case reports, 33% described experimental animal models, and 23.8% were opinion/review papers. Only two works included a placebo control group. The submission-to-publication interval (mean±standard deviation) was 130±96 days, there were 5.9±3.2 authors per project, and journals invoiced US $1,613±1,466 (range, $0–$3,860) for APCs. Conclusion: There was no correlation between APC and time to publish (Pearson’s r=–0.01). Abstract content was inconsistent; sample size and patient age were often missing, yet free full-text “open access” was available for most publications (59.5%). The NIH Clinical Trials portal lists eight registered studies on “ovarian rejuvenation,” of which two are actively recruiting patients, while four have been terminated or have an uncertain status. Two studies have concluded, with results from one posted to the NIH website. PRP and its derivatives for ovarian treatment show early promise, but require further investigation. Research is accelerating and should be encouraged, particularly placebo-controlled randomized clinical trials.

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices.
Contraception ; Counseling* ; Fertilization in Vitro* ; Humans ; Hysterectomy ; Laparoscopy ; Patient Selection ; Uterus

OBJECTIVE: This investigation examined data on unplanned pregnancies following hysteroscopic sterilization (HS). METHODS: A confidential questionnaire was used to collect data from women with medically confirmed pregnancy (n=103) registered after undergoing HS. RESULTS: Mean (+/-SD) patient age and body mass index (BMI) were 29.5+/-4.6 years and 27.7+/-6.1 kg/m2, respectively. Peak pregnancy incidence was reported at 10 months after HS, although <3% of unplanned pregnancies occurred within the first three months following HS. Mean (+/-SD) interval between HS and pregnancy was 19.6+/-14.9 (range, 2 to 84) months. Patients age > or =30 years and BMI <25 reported conception after HS somewhat sooner than younger patients, although the differences in time to pregnancy were not significant (P=0.24 and 0.09, respectively). The recommended post-HS hysterosalpingogram (to confirm proper placement and bilateral tubal occlusion) was obtained by 66% (68/103) of respondents. CONCLUSION: This report is the first to provide patient-derived data on contraceptive failures after HS. While adherence to backup contraception 3 months after HS can be poor, many unintended pregnancies with HS occur long after the interval when alternate contraceptive is required. Many patients who obtain HS appear to ignore the manufacturer's guidance regarding the post-procedure hysterosalpingogram to confirm proper device placement, although limited insurance coverage likely contributes to this problem. The greatest number of unplanned pregnancies occurred 10 months after HS, but some unplanned pregnancies were reported up to 7 years later. Age, BMI, or surgical history are unlikely to predict contraceptive failure with HS. Further follow-up studies are planned to capture additional data on this issue.
Body Mass Index ; Contraception ; Surveys and Questionnaires ; Female ; Fertilization ; Follow-Up Studies ; Humans ; Incidence ; Insurance Coverage ; Pregnancy ; Pregnancy, Unplanned* ; Sterilization* ; Time-to-Pregnancy

This study covers the 5-year interval prior to COVID-19 admission for an otherwise healthy 46,XX adolescent expanding the developmental characterization of an unusual convergence of amenorrhea and genetic mutations. The patient experienced rapid collapse of endogenous estradiol output followed by secondary amenorrhea at 13 years of age. Euploid, diffusely hypocellular bone marrow was present on biopsy, although anemia or reduced total immunoglobulin production was not identified. Bone density was 1.5 years below mean; multiple dental anomalies were also documented. While alterations in “master regulator” genes RUNX2, SALL1, and SAMD9 are usually diagnosed in early childhood when missed milestones, dysmorphic features, or chronic infection/immune impairment warrant cross-disciplinary evaluation, this study is the first known report to associate ovarian failure with adolescence with such variants. Immunoglobulin patterns, osseous histomorphology, dentition, hematology/renal screening, pelvic anatomy, ovarian reserve data, and thyroid findings are also correlated. Although severe pathology is typically encountered when any of these genes are disrupted alone, this longitudinal survey reveals that a mild phenotype can prevail if these 3 variants occur simultaneously. Periodic monitoring is planned given the unclassified status of this unique mutation set.