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

Sills, E. Scott,Obregon-Tito, Alexandra J.,Gao, Harry,McWilliams, Thomas K.,Gordon, Anthony T.,Adams, Catharine A.,Slim, Rima The Korean Society for Reproductive Medicine 2017 Clinical and Experimental Reproductive Medicine Vol.44 No.1

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.

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

Sills, E Scott,Walsh, David J,Jones, Christopher A,Wood, Samuel H The Korean Society for Reproductive Medicine 2015 Clinical and Experimental Reproductive Medicine Vol.42 No.3

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.

Hildegard E . Peplau : Leader , Practitioner , Academician , Scholar , and Theorist ( International Conference on Interpersonal Relationships in Community - based Mental Health Nursing )

(Grayce M . Sills) 이화여자대학교 간호과학연구소 1997 이화여자대학교 간호과학연구소 국제학술대회 Vol.- No.-

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

E. Scott Sills,Xiang Li,Samuel H. Wood,Christopher A. Jones 대한산부인과학회 2017 Obstetrics & Gynecology Science Vol.60 No.3

ObjectiveAlthough 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. MethodsThis 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. ResultsIn 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). ConclusionThis 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.

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

( E. Scott Sills ),( Gianpiero D. Palermo ) 대한산부인과학회 2016 Obstetrics & Gynecology Science Vol.59 No.4

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.

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

E. Scott Sills,Samuel H. Wood 대한생식의학회 2021 Clinical and Experimental Reproductive Medicine Vol.48 No.4

Objective: 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 $1,642±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.

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

( E. Scott Sills ),( Xiang Li ),( Christopher A. Jones ),( Samuel H. Wood ) 대한산부인과학회 2015 Obstetrics & Gynecology Science Vol.58 No.6

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 ≥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.

Five-Year Assessment of Multiple Gene Variants Associated with Bone Marrow Hypocellularity, Reduced Bone Density, and Ovarian Insufficiency in Adolescence

E. Scott Sills,Conor Harrity,Samuel H. Wood 대한골대사학회 2022 대한골대사학회지 Vol.29 No.4

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 conver- gence of amenorrhea and genetic mutations. The patient experienced rapid collapse of endogenous estradiol output followed by secondary amenorrhea at 13 years of age. Eu- ploid, 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 child- hood when missed milestones, dysmorphic features, or chronic infection/immune im- pairment warrant cross-disciplinary evaluation, this study is the first known report to as- sociate ovarian failure with adolescence with such variants. Immunoglobulin patterns, osseous histomorphology, dentition, hematology/renal screening, pelvic anatomy, ovar- ian 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.

지역사회 정신간호 페플로의 대인관계 이론적용 : 대인관계적 간호 의사소통 기술

(Grayce M . Sills) 이화여자대학교 간호과학연구소 1997 이화여자대학교 간호과학연구소 국제학술대회 Vol.- No.-

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

Liu, Jiaen,Sills, E. Scott,Yang, Zhihong,Salem, Shala A.,Rahil, Tayyab,Collins, Gary S.,Liu, Xiaohong,Salem, Rifaat D. The Korean Society for Reproductive Medicine 2012 Clinical and Experimental Reproductive Medicine Vol.39 No.2

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 d5. 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.