Progress in human ovarian rejuvenation: Current platelet-rich plasma and condensed cytokine research activity by scope and international origin / 대한생식의학회지

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.

Intraovarian vascular enhancement via stromal injection of platelet-derived growth factors: Exploring subsequent oocyte chromosomal status and in vitro fertilization outcomes / 대한생식의학회지

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.

Analysis of surgeries performed after hysteroscopic sterilization as tabulated from 3,803 Essure patient experiences

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.

Pathogenic variant in NLRP7 (19q13.42) associated with recurrent gestational trophoblastic disease: Data from early embryo development observed during in vitro fertilization / 대한생식의학회지

OBJECTIVE: To describe in vitro development of human embryos derived from an individual with a homozygous pathogenic variant in NLRP7 (19q13.42) and recurrent hydatidiform mole (HM), an autosomal recessive condition thought to occur secondary to an oocyte defect. METHODS: A patient with five consecutive HM pregnancies was genomically evaluated via next generation sequencing followed by controlled ovarian hyperstimulation, in vitro fertilization (IVF) with intracytoplasmic sperm injection, embryo culture, and preimplantation genetic screening. Findings in NLRP7 were recorded and embryo culture and biopsy data were tabulated as a function of parental origin for any identified ploidy error. RESULTS: The patient was found to have a pathogenic variant in NLRP7 (c.2810+2T>G) in a homozygous state. Fifteen oocytes were retrieved and 10 embryos were available after fertilization via intracytoplasmic sperm injection. Developmental arrest was noted for all 10 embryos after 144 hours in culture, thus no transfer was possible. These non-viable embryos were evaluated by karyomapping and all were diploid biparental; two were euploid and eight had various aneuploidies all of maternal origin. CONCLUSION: This is the first report of early human embryo development from a patient with any NLRP7 mutation. The pathogenic variant identified here resulted in global developmental arrest at or before blastocyst stage. Standard IVF should therefore be discouraged for such patients, who instead need to consider oocyte (or embryo) donation with IVF as preferred clinical methods to treat infertility.

Combined hysteroscopy-laparoscopy approach for excision of pelvic nitinol fragment from Essure contraceptive device: Role of intraoperative fluoroscopy for uterine conservation

We describe the successful removal of a pelvic contraceptive coil in a symptomatic 46-year-old patient who had Essure devices for four years, using a combined hysteroscopy-laparoscopy-fluoroscopy approach. Following normal hysteroscopy, at laparoscopy the right Essure implant was disrupted and its outer nitinol coil had perforated the fallopian tube. However, the inner rod (containing polyethylene terephthalate) had migrated to an extrapelvic location, near the proximal colon. In contrast, the left implant was situated within the corresponding tube. Intraoperative fluoroscopy was used to confirm complete removal of the device, which was further verified by postoperative computed tomography. The patient's condition improved after surgery and she continues to do well. This is the first report to describe this technique in managing Essure complications remote from time of insertion. Our case highlights the value and limitations of preoperative and intraoperative imaging to map Essure fragment location before surgery.

Contraceptive failure after hysteroscopic sterilization: Analysis of clinical and demographic data from 103 unplanned pregnancies

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 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.

Endometrial fluid associated with Essure implants placed before in vitro fertilization: Considerations for patient counseling and surgical management / 대한생식의학회지

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.

Irish public opinion on assisted human reproduction services: Contemporary assessments from a national sample / 대한생식의학회지

OBJECTIVE: To measure Irish opinion on a range of assisted human reproduction (AHR) treatments. METHODS: A nationally representative sample of Irish adults (n=1,003) were anonymously sampled by telephone survey. RESULTS: Most participants (77%) agreed that any fertility services offered internationally should also be available in Ireland, although only a small minority of the general Irish population had personal familiarity with AHR or infertility. This sample finds substantial agreement (63%) that the Government of Ireland should introduce legislation covering AHR. The range of support for gamete donation in Ireland ranged from 53% to 83%, depending on how donor privacy and disclosure policies are presented. For example, donation where the donor agrees to be contacted by the child born following donation, and anonymous donation where donor privacy is completely protected by law were supported by 68% and 66%, respectively. The least popular (53%) donor gamete treatment type appeared to be donation where the donor consents to be involved in the future life of any child born as a result of donor fertility treatment. Respondents in social class ABC1 (58%), age 18 to 24 (62%), age 25 to 34 (60%), or without children (61%) were more likely to favour this donor treatment policy in our sample. CONCLUSION: This is the first nationwide assessment of Irish public opinion on the advanced reproductive technologies since 2005. Access to a wide range of AHR treatment was supported by all subgroups studied. Public opinion concerning specific types of AHR treatment varied, yet general support for the need for national AHR legislation was reported by 63% of this national sample. Contemporary views on AHR remain largely consistent with the Commission for Assisted Human Reproduction recommendations from 2005, although further research is needed to clarify exactly how popular opinion on these issues has changed. It appears that legislation allowing for the full range of donation options (and not mandating disclosure of donor identity at a stipulated age) would better align with current Irish public opinion.

Array comparative genomic hybridization screening in IVF significantly reduces number of embryos available for cryopreservation / 대한생식의학회지

OBJECTIVE: During IVF, non-transferred embryos are usually selected for cryopreservation on the basis of morphological criteria. This investigation evaluated an application for array comparative genomic hybridization (aCGH) in assessment of surplus embryos prior to cryopreservation. METHODS: First-time IVF patients undergoing elective single embryo transfer and having at least one extra non-transferred embryo suitable for cryopreservation were offered enrollment in the study. Patients were randomized into two groups: Patients in group A (n=55) had embryos assessed first by morphology and then by aCGH, performed on cells obtained from trophectoderm biopsy on post-fertilization day 5. Only euploid embryos were designated for cryopreservation. Patients in group B (n=48) had embryos assessed by morphology alone, with only good morphology embryos considered suitable for cryopreservation. RESULTS: Among biopsied embryos in group A (n=425), euploidy was confirmed in 226 (53.1%). After fresh single embryo transfer, 64 (28.3%) surplus euploid embryos were cryopreserved for 51 patients (92.7%). In group B, 389 good morphology blastocysts were identified and a single top quality blastocyst was selected for fresh transfer. All group B patients (48/48) had at least one blastocyst remaining for cryopreservation. A total of 157 (40.4%) blastocysts were frozen in this group, a significantly larger proportion than was cryopreserved in group A (p=0.017, by chi-squared analysis). CONCLUSION: While aCGH and subsequent frozen embryo transfer are currently used to screen embryos, this is the first investigation to quantify the impact of aCGH specifically on embryo cryopreservation. Incorporation of aCGH screening significantly reduced the total number of cryopreserved blastocysts compared to when suitability for freezing was determined by morphology only. IVF patients should be counseled that the benefits of aCGH screening will likely come at the cost of sharply limiting the number of surplus embryos available for cryopreservation.

First experience with intracytoplasmic sperm injection for extreme oligozoospermia associated with Crohn's disease and 6-mercaptopurine chemotherapy / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To describe the reproductive outcome following intracytoplasmic sperm injection (ICSI) for male factor infertility associated with Crohn's disease and 6-mercaptopurine (6-MP) chemotherapy.</p><p><b>METHODS</b>The male partner of a couple suffered from severe Crohn's disease and received a 3-month course of 6-MP for this condition. Two spontaneous conceptions were established before 6-MP, although post-chemotherapy semen analysis found the sperm concentration to be 8,000/mL. In vitro fertilization (IVF) with ICSI and embryo transfer was performed.</p><p><b>RESULTS</b>The woman underwent an uncomplicated controlled ovarian hyperstimulation sequence using a combined rec-FSH+hMG protocol, following late luteal phase pituitary downregulation. This culminated in the retrieval of 18 oocytes, 11 of which were fertilized with ICSI. She later delivered a normal male infant without urogenital anomaly. Four nontransferred blastocysts were cryopreserved.</p><p><b>CONCLUSION</b>This report describes the first successful birth after ICSI for severe oligozoospermia associated with Crohn's disease and 6-MP therapy. We outline salient features of Crohn's disease, 6-MP pharmacology, and their relevance to human fertility.</p>