Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential.

Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through in vitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.

Surgical and Fertility Outcomes of Reduced-Port Robotic Myomectomy: A Single-Center Experience of 401 Cases.

Background: Reduced-port robotic myomectomy (RPRM) using Da Vinci® Xi™ is a good fertility-saving surgical option, but the surgical and fertility outcomes are unknown. Methods: This was a retrospective cohort study evaluating the feasibility of RPRM in an academic tertiary hospital setting. A total of 401 patients who underwent RPRM by a single operator between October 2017 and October 2021 were included. For RPRM, three ports are required: a 1.5 cm umbilical incision and two 0.8 cm incisions 8 cm lateral to the umbilicus. A single-port system was applied through the umbilicus, which also functioned as a working port. Unlike conventional robotic surgery, only three robot arms were utilized for the entire surgical procedure. Results: Surgical and fertility outcomes were assessed through medical records review and follow-up telephone contact. The mean age of patients at the time of surgery was 39.7 ± 6.0 years. The most common indication for surgery was menorrhagia (n = 128, 31.9%). The average number of myomas removed was 4.7 ± 4.1 (1-22), and the size was 7.8 ± 2.5 cm (2.5-16.0). The mean operation time was 103.7 ± 45.6 min. Postoperative complications were found in 9.7% (n = 39) of patients; the most common complication was transfusion (7.7%, n = 31). After surgery, 70 patients tried to conceive, and 56 became pregnant naturally or by assisted reproduction (56/70, 80.0%). The mean interval time from operation to conception was 13.5 ± 10.1 months. Among 56 who conceived, 44 gave birth (62.9%), five were still ongoing (7.1%), and seven had miscarriages (10.0%). Cesarean section was performed for most cases (43/44, 97.7%). Eight patients had obstetric complications (16.3%), but no uterine rupture was reported. Conclusions: RPRM, which provides the benefits of conventional robotic surgery along with favorable obstetric and cosmetic results, is a feasible option for patients with symptomatic uterine myomas who wish to conceive in the future.

An 8-mm trocar-site hernia at a drainage insertion site after a three-port robotic myomectomy: case report and review of literature.

Trocar site hernia is a rare, serious operation-related complication after robotic gynecologic surgery. Here, we present two 8-mm port-site hernia cases after three-port robotic myomectomy with a review of reported previous cases. In the first case, small bowel obstruction was found postoperatively due to herniation at the left mid-axillary line 8-mm trocar site. Small bowel herniation through the same site as the first case was found in the second case. Emergency exploration was performed in both cases by extending the left trocar site. There was no sign of bowel ischemia, and successful bowel reduction and hernia repair were done. Unlike previously reported cases, these cases occurred in a normal body mass index (BMI) patient (first case 20.28 kg/m2, second case BMI 24.80 kg/m2) and were pelvic drain insertion sites. These sites were the weak points of the abdominal muscle coverage. Therefore, the closure of 8-mm trocar sites should be considered.

Risk Factors for Infertility in Korean Women.

BACKGROUND: Female infertility is a crucial problem with significant implications for individuals and society. In this study, we explore risk factors for infertility in Korean women. METHODS: A total of 986 female patients who visited six major infertility clinics in Korea were recruited from April to December 2014. Fertile age-matched controls were selected from two nationwide survey study participants. Conditional logistic regression after age-matching was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of each risk factor for infertility. RESULTS: Women with a body mass index (BMI) < 18.5 kg/m² had 1.35 times higher odds of infertility (OR, 1.35; 95% CI, 1.03-1.77), while those with a BMI ≥ 25.0 kg/m² had even higher odds (OR, 2.06; 95% CI, 1.61-2.64) compared to women with a normal BMI (18.5 kg/m² ≤ BMI < 25 kg/m²). Ever-smokers exhibited 4.94 times higher odds of infertility compared to never-smokers (95% CI, 3.45-8.85). Concerning alcohol consumption, women who consumed ≥ 7 glasses at a time showed 3.13 times significantly higher odds of infertility than those who consumed ≤ 4 glasses at a time (95% CI, 1.79-5.48). Lastly, women with thyroid disease demonstrated 1.44 times higher odds of infertility compared to women without thyroid disease (95% CI, 1.00-2.08). CONCLUSION: Female infertility in Korea was associated with underweight, obesity, smoking, alcohol consumption, and thyroid disease.

A Successful Live Birth From a Vitrified Oocyte for Fertility Preservation of a Patient With Borderline Ovarian Tumor Undergoing Bilateral Ovarian Surgery: A Case Report.

This article reports the live birth of a healthy newborn using vitrified-warmed oocytes from fertility preservation before ovarian surgery. The patient in our case underwent two cycles of controlled ovarian stimulation before laparoscopic bilateral ovarian cystectomy for endometriosis, and a total of 23 mature oocytes were vitrified. After surgery, her pathologic reports revealed a serous borderline tumor and endometrioma. Fifteen months after her second surgery of laparoscopic right salpingo-oophorectomy and left ovarian cystectomy owing to recurrence, she had been married by then, and three of the frozen oocytes were thawed for intracytoplasmic sperm injection. These oocytes were cryopreserved for 2.5 years. All three were fertilized, and two grade-A cleavage-stage embryos were transferred. A singleton pregnancy was achieved, resulting in the delivery of a healthy baby boy at 39.3 weeks of gestation. Oocyte cryopreservation is an effective method for fertility preservation prior to ovarian surgery when ovarian function decline is predictable.

Thiol-yne click crosslink hyaluronic acid/chitosan hydrogel for three-dimensional in vitro follicle development.

There is a great deal of potential for in vitro follicle growth to provide an alternative approach to fertility preservation. This strategy reduces the possibility of cancer cells re-exposure after transplantation, and it does not require hormone stimulation. Adopting a three-dimensional (3D) culture method helps preserve the architecture of the follicle and promotes the maturity of oocytes. In order to maintain follicle morphology, enhance the quality of mature oocytes, and facilitate meiotic spindle assembly, the current work aimed to develop the 3D in vitro preantral mouse follicle culture method. Thiolated chitosan-co-thiolated hyaluronic (CSHS) hydrogel was designed to evaluate the effects of biomaterials on ovarian follicle development. Isolated follicles from mouse ovaries were randomly divided into alginate (Alg) as a 3D control, thiolated hyaluronic acid (HASH), and CSHS groups. Single follicle was encapsulated in each hydrogel, and performed for 10 days and subsequently ovulated to retrieve mature oocytes on day 11. CSHS hydrogel promoted follicle survival and oocyte viability with maintained spherical morphology of follicle. Matured oocytes with normal appearance of meiotic spindle and chromosome alignment were higher in the CSHS group compared with those in the Alg and HASH groups. Furthermore, CSHS increased expression level of folliculogenesis genes (TGFß-1, GDF-9) and endocrine-related genes (LHCGR, and FSHR). With various experimental setups and clinical applications, this platform could be applied as an alternative method to in vitro follicle culture with different experimental designs and clinical applications in the long-term period.