A systematic review of uterine cervical elongation and meta-analysis of Manchester repair.

OBJECTIVE: This review aims to consolidate current research on cervical elongation, a common but often overlooked complication in pelvic organ prolapse and hysteropexy procedures. It seeks to define, diagnose, and manage cervical elongation, aiming to establish standardized criteria and strategies to enhance clinical outcomes for this condition. DATA SOURCES: A comprehensive search of the PubMed/MEDLINE, Cochrane Library, and Web of Science databases was executed utilizing the keywords: "cervical elongation," "long cervix uteri," "Manchester," and "cervical amputation". Data were gathered and organized in an Excel spreadsheet, with the analysis conducted according to each category, methodology, or reference range. STUDY ELIGIBILITY CRITERIA: All types of study designs with full-text availability, including randomized controlled trials, cohort studies, case-control studies, case reports, and systematic reviews, were considered for inclusion. Included studies were fully accessible in English and focused on the topic of interest. Exclusions were made for studies addressing cervical elongation not pertinent to pelvic organ prolapse, and publications such as secondary analyses, case reports, literature reviews, and opinion papers. RESULTS: Out of 108 relevant studies, only 63 defined their inclusion criteria; of these, 57 were utilized for the narrative review and 8 were used in a meta-analysis comparing the Manchester operation with vaginal hysterectomy. Magnetic Resonance Imaging offers the highest sensitivity in measuring cervical elongation, its practical limitations and high cost necessitate the use of the more feasible Pelvic Organ Prolapse Quantification System (POP-Q), particularly effective for stage 2 and 3 prolapse cases. The POP-Q point C emerges as a pivotal marker for identifying cervical elongation, with specific measurements indicating the condition's presence. The Manchester-Fothergill procedure presents a viable management option for isolated cervical elongation, showing fewer complications and comparable recurrence rates to vaginal hysterectomy. CONCLUSION: This review highlights the diagnostic and definitional diversity of cervical elongation within populations experiencing pelvic organ prolapse. It emphasizes the critical role of preoperative cervical evaluation, particularly in patients with uterine descensus for selecting the most appropriate surgical intervention.

Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern.

This study intended to investigate if gynecological cancers compromise ovarian function and reduce the success of assisted reproduction techniques (ART). No clinical and molecular data together is available on this issue for gynecological or other organ cancers. Steroidogenic pathways and DNA damage response characteristics of the granulosa cells retrieved from the 39 gynecological cancer patients were analyzed together with their clinical ART characteristics in comparison to 31 control ART patients. Patients with gynecological malignancies were similar to the control IVF patients for the number of mature oocytes retrieved, fertilization rates and embryo development competency. Molecular analyses of the granulosa cells retrieved from these cancer patients did not detect any perturbations in gonadotropin receptor expression and response, sex steroid production, cholesterol utilization/storage and, DNA damage response pattern in comparison to control IVF patients without cancer. This study provides the first reassuring clinical and molecular combined data set that the presence of gynecological malignancy does not appear to have any detrimental effect on clinical IVF cycle characteristics and ovarian functioning at molecular level.

Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Fertility and anatomical outcomes following hysteroscopic adhesiolysis: An 11-year retrospective cohort study to validate a new classification system for intrauterine adhesions (Urman-Vitale Classification System).

OBJECTIVE: To propose a new classification system (Urman-Vitale Classification System) for intrauterine adhesions (IUAs) and to evaluate anatomical and fertility outcomes after hysteroscopic adhesiolysis accordingly. METHODS: A retrospective analysis of consecutive patients treated over 11 years by a single operator in a tertiary care hospital. Women with sonographic suspicion of IUAs were scheduled for hysterosalpingography (HSG) and hysteroscopy for confirmation and treatment. IUAs were divided into five classes according to symptoms, ultrasound, HSG findings, and postsurgical hysteroscopic appearance. Hysteroscopic adhesiolysis was performed using a bipolar cutting electrode in an office setting. Evaluated outcomes were restoration of the uterine cavity, clinical pregnancy, pregnancy loss, and live birth rates. RESULTS: A total of 227 patients (479 procedures) were included. Mean number of hysteroscopies increased in frequency with class of adhesions from Class 1 to Class 5 (1.0 ± 0.2 vs 2.3 ± 0.5; P = 0.001). Full restoration of the cavity was achieved in 100% of patients with Class 1 compared with 18.5% for Class 5 (43/43 vs 5/27; P = 0.001). Clinical pregnancy (Class 1 vs Class 4: P = 0.034; 1 vs 5: P = 0.006; 2 vs 5: P = 0.024) and live birth (Class 1 vs Class 4: P = 0.001; 1 vs 5: P = 0.006; 2 vs 4: P = 0.007; 2 vs 5: P = 0.0208) rates decreased with increasing severity of IUAs. Pregnancy loss rate was related to IUA severity (Class 1 vs Class 4: P = 0.012; 1 vs 5: P = 0.003: 2 vs 4: P = 0.014; 2 vs 5: P = 0.021). CONCLUSION: A classification based on symptoms, imaging findings, and postsurgical macroscopic appearance of the uterine cavity could be useful in predicting prognosis and fertility in women with IUAs.

Hysteroscopic Endometrial Ablation: From Indications to Instrumentation and Techniques-A Call to Action.

The development of minimally invasive techniques has led to the creation of innovative alternatives in cases where traditional methods are not applicable. In modern gynecology, hysteroscopy has become the gold standard for the evaluation and treatment of intrauterine pathology. Endometrial ablation (EA) is a procedure that uses different types of energy to destroy the endometrium and is currently used as an alternative technique in cases of heavy menstrual bleeding when medical treatment has failed and uterine preservation is desired. The aim of this review was to evaluate the feasibility, safety, and clinical outcomes of hysteroscopic EA as an alternative in patients with abnormal uterine bleeding. A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane Library), from 1994 to June 2022, to evaluate the outcomes in patients with abnormal uterine bleeding (AUB) undergoing EA using hysteroscopic and non-hysteroscopic techniques. Only scientific publications in English were included. Twelve articles on the current use of endometrial ablation were included. Data on patient symptoms, tools used for EA, primary outcomes, and adverse events were recorded. EA should be considered an effective and safe approach in the management of patients with abnormal uterine bleeding caused by benign pathology, in whom medical treatment has failed or is contraindicated. Due to the lack of evidence, it would be interesting to determine whether EA would also have a role in the treatment of women with premalignant lesions, avoiding invasive surgical procedures or medical treatment in those patients for whom hysterectomy or the use of hormonal treatment is contraindicated.

Abnormal Uterine Bleeding in Perimenopausal Women: The Role of Hysteroscopy and Its Impact on Quality of Life and Sexuality.

Abnormal uterine bleeding (AUB) is a frequent symptom in perimenopausal women. It is defined as uterine bleeding in which the duration, frequency, or amount of bleeding is considered excessive and negatively affects the woman's quality of life (QoL) and psychological well-being. In cases of structural uterine pathology, hysterectomy (usually performed via a minimally invasive approach) offers definitive symptom relief and is associated with long-lasting improvement of QoL and sexuality. However, over the past 30 years, uterus-preserving treatments have been introduced as alternatives to hysterectomy. Hysteroscopic polypectomy, myomectomy, or endometrial resection/endometrial ablation are minimally invasive techniques that can be used as an alternative to hysterectomy to treat AUB due to benign conditions. Although associated with high patient satisfaction and short-term improvement in their QoL, hysteroscopic treatments do not eliminate the risk of AUB recurrence or the need for further intervention. Therefore, considering the impact of different treatment options on QoL and sexuality during preoperative shared decision making could help identify the most appropriate and personalized treatment options for perimenopausal women suffering from AUB.

The role of hysteroscopy in reproductive surgery: Today and tomorrow.

During the last decades, the number of couples with reproductive issues has substantially increased. Many different factors are implicated in reproductive failure, including uterine factors. Endometrial pathologies, such as endometrial polyps, hyperplasia, endometritis, and Mullerian anomalies, can also hinder embryo implantation. Hysteroscopy remains the gold standard for the evaluation and treatment of intrauterine pathology. Over the last few years, advances in hysteroscopic instrumentations and surgical techniques have significantly evolved, the refinement in technology, miniaturization of instruments, and improved image quality have rendered hysteroscopy a more patient and user-friendly procedure that has enhanced its use in reproductive medicine. Nowadays, hysteroscopy is essential in the evaluation and treatment of women with infertility. This article underscores the major technological breakthroughs achieved over the last few years with emphasis on the role of artificial intelligence, augmented reality, and 3D hysteroscopy, which can set new benchmarks in hysteroscopy applied to reproductive medicine.

Mini-plus percutaneous setting in total laparoscopic hysterectomy.

INTRODUCTION: We aimed to analyze the preliminary experience of a mini-plus percutaneous instrument (MpPc) setting in total laparoscopic hysterectomy (TLH). MATERIAL AND METHODS: Forty-three women who underwent a mini-plus percutaneous total laparoscopic hysterectomy at a tertiary-care university-based teaching hospital and academic affiliated private hospital between May 2017 and 2018 were included. MpPc-TLH was performed through one optical trans-umbilical 5-mm trocar, one 5-mm ancillary port on the right side, either one 2.4-mm percutaneous endoscopic instrument or 3-mm mini-laparoscopic port on the right upper quadrant and if required one 3-mm ancillary port on the left lower quadrant. RESULTS: A total of 43 patients were included, with a median age of 48 years (range, 38-71 years). Indication for surgery included uterine myomas (n = 20), benign adnexal mass (n = 7), endometrial intraepithelial neoplasia (n = 6), endometrial cancer (n = 5), adenomyosis with abnormal bleeding (n = 3), and high-grade cervical dysplasia (n = 2). The median operating time was 100 min (range, 60-180 min), and the median estimated blood loss was 30 ml (range, 20-60ml). The median postoperative abdominal pain Visual Analog Scale score was 3 (range, 0-6). CONCLUSIONS: The preliminary data suggest that MpPc approach is a feasible and safe surgical modality for total laparoscopic hysterectomy.

Mini-Laparoscopic Gynecological Surgery Using Smaller Ports Minimizes Incisional Pain and Postoperative Scar Size: A Paired Sample Analysis.

Objective. The aim of this study was to assess postoperative incisional pain and cosmetic scores in mini-laparoscopic gynecological surgeries undertaken with different port sizes. Material and Method. In this prospective study, all women who underwent mini-laparoscopic gynecological surgery with 2.4-, 3-, and 5-mm lateral ports for benign gynecological conditions between March 2017 and April 2019 were included. The primary outcome was postoperative incisional pain at rest, walking, and after a provoked Valsalva maneuver assessed by numeric rating scale scores at 6 hours, 12 hours, 24 hours, and 3 days and 7 days after surgery. Secondary outcome measures included cosmetic scores of each port site (evaluated by using patient-observer scar assessment scale [POSAS]), operation time, and intra- and postoperative complications. Results. A total of 330 lateral port sites in 110 patients who underwent benign gynecological surgery via mini-laparoscopy were assessed for pain and cosmetic appearance. Pain scores at each time point were significantly lower for 2.4- and 3-mm ports than those for 5-mm ports; however, no significant difference was detected between 2.4-mm and 3-mm port sites (P = .6). The difference was more evident at 24 hours when routine analgesic drugs were stopped (P = .004). For POSAS scores, both 2.4-mm and 3-mm ports were superior to 5-mm port sites (P = .002); however, there was no significant difference between 2.4-mm and 3-mm port sites (P = .2). There were 2 port-related complications: one subcutaneous emphysema and one bleeding from a 5-mm trocar site 1 hour after surgery. Conclusion. Mini-laparoscopic gynecologic surgery using smaller ports resulted in decreased postoperative incisional pain and superior cosmetic appearance.

hCG Improves Luteal Function and Promotes Progesterone Output through the Activation of JNK Pathway in the Luteal Granulosa Cells of the Stimulated IVF Cycles†.

Human chorionic gonadotropin (hCG) is a luteotropic hormone that promotes the survival and steroidogenic activity of corpus luteum (CL) by acting through luteinizing hormone receptors (LHRs) expressed on luteinized theca and granulosa cells (GCs). Therefore, it is used to support luteal phase in in vitro fertilization (IVF) cycles to improve clinical pregnancy rates and prevent miscarriage. However, the molecular mechanism underlying this action of hCG is not well characterized. To address this question, we designed an in vitro translational research study on the luteal GCs obtained from 58 IVF patients. hCG treatment at different concentrations and time points activated c-Jun N-terminal kinase (JNK) pathway and significantly increased its endogenous kinase activity along with upregulated expression of steroidogenic enzymes (steroidogenic acute regulatory protein (stAR), 3ß-Hydroxysteroid dehydrogenase (3ß-HSD)) in a dose-dependent manner in the luteal GCs. As a result, in vitro P production of the cells was significantly enhanced after hCG. When JNK pathway was inhibited pharmacologically or knocked-down with small interfering RNA luteal function was compromised, P4 production was declined along with the expression of stAR and 3ß-HSD in the cells. Further, hCG treatment after JNK inhibition failed to correct the luteal defect and promote P4 output. Similar to hCG, luteinizing hormone (LH) treatment improved luteal function as well and this action of LH was associated with JNK activation in the luteal GCs. These findings could be important from the perspective of CL biology and luteal phase in human because we for the first time identify a critical role for JNK signaling pathway downstream LHR activation by hCG/LH in luteal GCs. SUMMARY SENTENCE: JNK signaling pathway plays a central role in the upregulated expression of the steroidogenic enzymes StAR and 3b-HSD and augmented progesterone production by hCG/LH in human luteal granulosa cells.

Platelet-rich plasma another add-on treatment getting out of hand? How can clinicians preserve the best interest of their patients?

Add-on treatments in IVF are utilized to a great extent but without sufficient evidence showing their effectiveness. Since the offered treatments are usually costly and may be associated with yet unknown risks, this practice is not in the best interest of couples that may go to great lengths to conceive and have an offspring carrying their own genetic make-up. A recent addition to this armamentarium is the administration of platelet-rich plasma (PRP) in women with diminished ovarian reserve, implantation failures, and a thin endometrium. The only evidence for PRP comes from small scale and mostly before and after studies with clinically irrelevant end points. PRP has not been subjected to a rigorous clinical trial. It is a typical example of an add-on gaining widespread popularity based on biological plausibility and mind-bending theoretical presumptions. We should be extremely cautious prior to implementing PRP on a widescale and await the results of well-designed studies.

Comparison of a novel flexible progestin primed ovarian stimulation protocol and the flexible gonadotropin-releasing hormone antagonist protocol for assisted reproductive technology.

OBJECTIVE: To determine whether a flexible progestin primed ovarian stimulation (fPPOS) protocol is effective for preventing premature ovulation. DESIGN: Retrospective cohort study. SETTING: Private assisted reproduction center. PATIENT(S): Eighty-seven oocyte donors and 191 recipients of fresh oocytes. INTERVENTION(S): Each donor was stimulated with a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in one cycle and with the new fPPOS protocol in the other, within a period of 6 months. FSH was started on cycle day 2-3, and 0.25 mg/day GnRH antagonist or 10 mg/day medroxyprogesterone acetate (MPA) was started on stimulation day 7 or when the leading follicle reached 14 mm, whichever came first. MAIN OUTCOME MEASURE(S): Duration of stimulation, gonadotropin consumption, duration of GnRH antagonist or MPA administration, number of metaphase II oocytes, and pregnancy rates in fresh oocyte recipients. RESULTS: Duration of stimulation was 11 (10-11) days in both groups. Total gonadotropin consumption was similar. Pituitary suppression was started on day 7 and lasted for 5 days in each group. There were no premature ovulations in any group. The fPPOS yielded a significantly higher number of cumulus oocyte complexes than GnRH antagonist cycles (33 [21-39] vs. 26 [18-36], respectively). Likewise, the fPPOS generated significantly more metaphase II oocytes than GnRH antagonist cycles (24 [17-34] vs. 21 [15-28], respectively). Recipients of fresh oocytes from fPPOS and GnRH antagonist cycles had similar cleavage, blastulation, implantation, and live birth/ongoing pregnancy rates (50% vs. 48.6%). CONCLUSION(S): FPPOS with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality.

The Endobiota Study: Comparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 Endometriosis and Healthy Controls.

Dysbiosis in the genital tract or gut microbiome can be associated with endometriosis. We sampled vaginal, cervical and gut microbiota from 14 women with histology proven stage 3/4 endometriosis and 14 healthy controls. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. Despite overall similar vaginal, cervical and intestinal microbiota composition between stage 3/4 endometriosis group and controls, we observed differences at genus level. The complete absence of Atopobium in the vaginal and cervical microbiota of the stage 3/4 endometriosis group was noteworthy. In the cervical microbiota, Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma, all of which contain potentially pathogenic species, were increased in stage 3/4 endometriosis. More women in the stage 3/4 endometriosis group had Shigella/Escherichia dominant stool microbiome. Further studies can clarify whether the association is causal, and whether dysbiosis leads to endometriosis or endometriosis leads to dysbiosis.

Clermont-Ferrand versus Vectec uterine manipulator for total laparoscopic hysterectomy.

OBJECTIVE: To compare the operation time and performance of two uterine manipulators used for total laparoscopic hysterectomy (TLH). MATERIAL AND METHODS: Design: Retrospective cohort analysis. Design classification: Canadian Task Force Classification II-2. SETTING: Tertiary-care university-based teaching hospital and academic affiliated private hospital. PATIENTS: All consecutive patients who underwent for TLH between January 2014 and June 2017. All operations were performed by two expert endoscopic surgeons using one of the following uterine manipulators depending on surgeon preferences: Clermont-Ferrand (CF) or Vectec (VT) MAUT60. Patients were excluded if additional surgeries such as urogynecological procedures were performed, TLH was converted to laparotomy prior to colpotomy, and when their operation records could not be obtained. A total of 169 patients were added to final analysis. Operation time, colpotomy time and the subjective performance of manipulators such as movement of the uterus, visualization of the vaginal fornices, and maintenance of pneumoperitoneum were evaluated by watching un-edited operation videos. RESULTS: A total of 169 patients (83 patients in CF group; 86 patients in VT group) were included in the final analysis. Patients' baseline characteristics were comparable between groups. Operation time and time required for colpotomy were significantly shorter in the VT group. Lateral movements of the manipulators and elevation of the uterus were better with VT compared to CF (p = .001 for both). Compared to the CF, VT was superior for visualization of the vaginal fornices (p = .004) and maintenance of pneumoperitoneum (p < .001). Both surgeons had perfect agreement on the performance grading of manipulators (p < .001, Kappa values were between 0.86-0.92). There was no difference between groups in estimated blood loss and duration of hospital stay. Reinsertion or the need to change the manipulator was not required in either group. No pelvic or vaginal abscess, cuff cellulitis, dehiscence, or hematoma formations were noted. CONCLUSION: Laparoscopic hysterectomy assisted with the VT uterine manipulator is associated with shorter operation and colpotomy time. Furthermore, the movements of uterus, visualization of the vaginal fornices, and maintenance of pneumoperitoneum were significantly better with VT compared to the CF manipulator.

Contained Power Morcellation Versus Transvaginal Extraction for Retrieval of Laparoscopically Removed Myomas: A Comparison of Perioperative Outcomes.

OBJECTIVE: To evaluate clinical and operative outcomes of transvaginal extraction (TVE) and contained power morcellation (CPM) for myoma retrieval after laparoscopic myomectomy. MATERIALS AND METHODS: Prospective data from 35 consecutive cases using CPM were compared with retrospective data of all cases using TVE from December 2014 to January 2017. Patients were matched 1:1 based on myoma diameter. A total of 62 women were included in the final analysis. Specimen retrieval was performed using the TVE or CPM within an insufflated isolation bag. RESULTS: Age, body mass index, mode of prior obstetric delivery, history of previous abdominal surgery, indication for myomectomy, and the myoma(s) characteristics were similar between groups. Retrieval time was significantly shorter in the TVE group compared with the CPM group: 10 minutes (3-15 minutes) versus 17 minutes (14-42 minutes); P < .001. Time required for placement of the instruments was 9.7 minutes for the isolation bag and 0.5 minutes for the vaginal extractor. Additional analgesic administration for pain relief was necessary in 13 patients (42%) in the TVE group and 23 patients (72%) in the CPM group ( P = .01). Total cost of the hospital stay was significantly higher in the CPM group compared with the TVE group ( P < .001). Estimated blood loss and duration of hospital stay were similar between groups. CONCLUSION: Both CPM and TVE can be used for safe retrieval of large myomas that are removed laparoscopically. Compared with CPM, TVE was associated with a shorter retrieval time, less postoperative pain, and less hospital costs.

Luteal granulosa cells from natural cycles are more capable of maintaining their viability, steroidogenic activity and LH receptor expression than those of stimulated IVF cycles.

STUDY QUESTION: Are there any differences in the molecular characteristics of the luteal granulosa cells (GC) obtained from stimulated versus non-stimulated (natural) IVF cycles that may help explain the defective luteal phase in the former? SUMMARY ANSWER: Luteal GC of stimulated IVF cycles, particularly those of agonist-triggered antagonist cycles, are less viable ex vivo, express LH receptor and anti-apoptotic genes at lower levels, undergo apoptosis earlier and fail to maintain their estradiol (E2) and progesterone (P4) production in comparison to natural cycle GC. WHAT IS KNOWN ALREADY: Luteal function is defective in stimulated IVF cycles, which necessitates P4 and/or hCG administration (known as luteal phase support) in order to improve clinical pregnancy rates and prevent miscarriage. The luteal phase becomes shorter and menstruation begins earlier than a natural cycle if a pregnancy cannot be achieved, indicative of early demise of corpus luteum (premature luteolysis). Supra-physiological levels of steroids produced by multiple corpora luteae in the stimulated IVF cycles are believed to inhibit LH release directly via negative feedback actions on the hypothalamic-pituitary-ovarian axis resulting in low circulating levels of LH and a defective luteal phase. We hypothesized that some defects in the viability and steroidogenic activity of the luteal GC of the stimulated IVF cycles might contribute to this defective luteal phase in comparison to natural cycle GC. This issue has not been studied in human before. STUDY DESIGN, SIZE, DURATION: A comparative translational research study of ex vivo and in vitro models of luteal GC recovered from IVF patients undergoing natural versus stimulated IVF cycles was carried out. Luteinized GC were obtained from 154 IVF patients undergoing either natural (n = 22) or stimulated IVF cycles with recombinant FSH and GnRH agonist (long) (n = 44), or antagonist protocol triggered conventionally either with recombinant hCG (n = 46) or with a GnRH agonist (n = 42). GC were maintained in vitro for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cellular viability (YO-PRO-1 staining), the expression of the steroidogenic enzymes, pro-apoptotic genes [Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX) and Caspase-3 (CASP3)], anti-apoptotic genes [RAC-alpha serine/threonine-protein kinase (AKT-1) and Bcl-2-like protein 2 (BCL2-L2)], LH receptor, vascular endothelial growth factor (VEGF) (using real-time quantitative PCR at mRNA level and western blot immunoprecipitation assay at protein level) and in vitro E2 and P4 production (electrochemiluminescence immunoassay) were compared in GC among the groups. MAIN RESULTS AND THE ROLE OF CHANCE: Natural cycle GC were significantly more viable ex vivo (88%) compared to their counterparts of the stimulated IVF cycles (66, 64 and 37% for agonist and antagonist cycles triggered with hCG and GnRH agonist respectively, P < 0.01). They were also more capable of maintaining their vitality in culture compared to their counterparts from the stimulated IVF cycles: at the end of the 6-day culture period, 74% of the cells were still viable whereas only 48, 43 and 22% of the cells from the agonist and antagonist cycles triggered with hCG and agonist respectively, were viable (P < 0.01). The mRNA expression of anti-apoptotic genes (AKT-1 and BCL2-L2) was significantly lower, while that of pro-apoptotic genes (BAD, BAX and CASP3) was significantly higher in the stimulated cycles, particularly in the agonist-triggered antagonist cycles, compared to natural cycle GC (P < 0.01 for long protocol and antagonist hCG trigger, P < 0.001 for agonist trigger). The expression of steroidogenic enzymes (stAR, SCC, 3ß-HSD and aromatase) and VEGF was significantly higher in the agonist and hCG-triggered antagonist cycles compared to natural cycle GC. Therefore, in vitro E2 and P4 production in cells from the stimulated IVF cycles was significantly higher than their counterparts obtained from the natural cycles in the first 2 days of culture. However, after Day 2, their viability and hormone production began to decline very rapidly with the most drastic decrease being observed in the agonist-triggered cycles. By contrast, natural cycle GC maintained their viability and produced E2 and P4 in increasing amounts in culture up to 6 days. In vitro P production and the mRNA and protein expression of LH receptor, VEGF and 3ß-HSD were most defective in the agonist-triggered antagonist cycles compared to natural and agonist and hCG-triggered antagonist cycles. In vitro hCG treatment of a subset of the cells from the agonist-triggered cycles improved their viability, increased E2 and P4 production in vitro and up-regulated the mRNA expression of anti-apoptotic gene BCL-L2 together with steroidogenic enzymes stAR, SCC, 3B-HSD, LH receptor and VEGF. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The limitations include analysis of luteinized GC only might not reflect the in vivo mechanisms involved in survival and function of the whole corpus luteum; GC recovered during oocyte retrieval belong to a very early stage of the luteal phase and might not be representative; effects of ovulation triggered with hCG may not equate to the endogenous LH trigger; the clinical characteristics of the patients may vary among the different groups and it was not possible to correlate stimulation-related molecular alterations in luteal GC with the clinical outcome, as no oocytes have been utilized yet. Therefore, our findings do not conclusively rule out the possibility that some other mechanisms in vivo may also account for defective luteal function observed in stimulated IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian stimulation is associated with significant alterations in the viability and steroidogenic activity of luteal GC depending on the stimulation protocol and mode of ovulation trigger. Reduced survival and down-regulated expression of 3B-HSD, LH receptor and VEGF leading to compromised steroid production in stimulated cycles, and particularly in the agonist-triggered cycles, may at least in part help explain why the luteal phase is defective and requires exogenous support in these cycles. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest.

Surgical correction of T-shaped uteri in women with reproductive failure: Long term anatomical and reproductive outcomes.

OBJECTIVE: To evaluate the long term anatomical and reproductive outcomes of hysteroscopic treatment for T shaped uterus in patients presenting with reproductive failure. METHODS: This prospective cohort study included 56 patients with a history of long-standing unexplained infertility, recurrent implantation failure (RIF), and/or recurrent pregnancy loss (RPL) who were eligible for metroplasty by office hysteroscopy. Office hysteroscopy under conscious sedation was performed. Anatomical outcomes were assessed with pre- and postoperative measurements of the transostial, isthmic and myometrial diameters and the uterine volume using three-dimensional transvaginal sonography (3D-TVS). Reproductive outcome was assessed after spontaneous or assisted conception. RESULTS: Hysteroscopic treatment significantly increased the volume of the uterus from a mean of 2.5+1mL before surgery to 3.2±1mL by the end of 1 year as measured by 3D-TVS. According to the main indication to perform metroplasty, 20 of 32 (62.5%) patients with long standing unexplained infertility, 9 of 14 (64%) patients with RIF, and 8 of 10 (80%) patients with RPL conceived either spontaneously or with assisted reproduction. CONCLUSIONS: Office hysteroscopic metroplasty results in a significant long-term expansion of the uterine cavity and improved reproductive outcomes in women presenting with a T shaped uterus and poor reproductive history.

High responders are not exempt from detrimental effects of prematurely rising progesterone levels in fresh embryo transfer cycles.

RESEARCH QUESTION: Are high-responder IVF patients protected from the deleterious effect of prematurely elevated serum progesterone level on the probability of pregnancy? DESIGN: In this retrospective cohort study, 2971 autologous fresh embryo transfer IVF cycles with gonadotrophin-releasing hormone agonist long protocol were analysed to investigate whether the detrimental effect of prematurely rising progesterone levels on clinical pregnancy rate (CPR) varies depending on the magnitude of ovarian response. Nine different evenly spaced intervals were constructed for serum progesterone level on the human chorionic gonadotrophin day (<0.5/0.5-0.9/1-1.4/1.5-1.9/2-2.4/2.5-2.9/3-3.4/3.5-3.9/>4 ng/ml). Then, IVF cycles in each of these intervals were further divided into low (≤3 oocytes), normal (4-15 oocytes) and high responders (≥16 oocytes). RESULTS: The progressive rise of serum progesterone from the <0.5 to the >4 ng/ml interval caused a gradual and continuous decline in the CPR of all three types of ovarian response. The absolute difference in the CPR between the lowest and the highest progesterone groups was not related to the magnitude of ovarian response (-26.6%, -37.7% and -40.7% for the low, normal and high responders, respectively). On multivariate logistic regression analysis, the detrimental effect of progesterone started at 1.5-1.9 ng/ml, 3.0-3.4 ng/ml and 4.0-4.4 ng/ml intervals for the low, normal and high responders, respectively. CONCLUSION: High responders are not exempt from the detrimental effects of prematurely rising serum progesterone levels but the threshold interval where the detrimental effect begins is higher in the high responders compared with the low and normal responders.

Use of a gelatin-thrombin hemostatic matrix in obstetrics and gynecological surgery.

Gelatin-thrombin matrix (GTM) is a hemostatic sealant consisting of bovine-derived gelatin matrix and human-derived thrombin, combining both mechanical and active mechanisms to achieve hemostasis. It was approved by the Food and Drug Administration in 1999. GTM has been used by several surgical specialties; however, it is a possibly an under-used tool in obstetrics and gynecology. A limited number of studies have been performed on its use during laparoscopic endometrioma excision and myomectomy. It may prove useful in endometrioma excision in reproductive aged women because it is likely to harm ovarian reserve less than electrocautery; however, this conclusion needs to be validated. The only study on GTM use in myomectomy included 50 women randomized into GTM and control groups, and showed decreased blood loss and shorter hospital stays in the GTM group. In gynecologic oncology, it was successfully used to reduce lymphocele cases in a cohort study. GTM has been used successfully in obstetrics in a handful of cases of uncontrolled bleeding from caesarean scar, placental site, ectopic pregnancy, rectovaginal hematoma, and venous plexus over the vaginal vault after emergency postpartum hysterectomy. Risk of viral transmission is a major concern about GTM, yet there are no reports on disease transmission with GTM use to date. Rare but serious adverse effects and complications have been reported such as fatal or near-fatal thromboembolism and small bowel obstruction. Although GTM is mostly a safe product, it is still not free of complications and risks. In conclusion, although routine use of GTM cannot be recommended due to concerns about its safety, cost, and availability, it may prove useful when conventional hemostatic methods such as suturing and electrocauterization fail or are not appropriate.

Unidirectional barbed suture for vaginal cuff closure without backward stitch in total laparoscopic hysterectomy.

AIM: To evaluate the safety and efficacy of unidirectional barbed suture technique for vaginal cuff closure in total laparoscopic hysterectomy (TLH). METHODS: In a retrospective chart review, data were analyzed from 165 patients who underwent a TLH with an unidirectional barbed suture technique for vaginal cuff closure from January 2012 to June 2016 at tertiary-care university-based teaching hospital and academic affiliated hospital. Vaginal cuff was closed by single layer 3/0 V-Loc unidirectional 9″, 180 day Absorbable Wound Closure Device (Covidien Healthcare, Mansfield, MA) and the suture was not stitched backward to secure distal end. RESULTS: A total of 165 patients were included and the median age was 50 years (range, 35-84 years). The median completion time for hysterectomy time was 100 min (range, 40-240 min) and the median vaginal cuff closure time was 7 min (range, 4-15 min). The median estimated blood loss was 87.8 mL (range 30-250 mL) and the median uterine weight was 200 g (range, 40-900 g). Intraoperative complication included bladder perforation (1.2%) and postoperative complications were vaginal cuff dehiscence (1.8%), cuff cellulitis (0.6%), vesicovaginal fistula (0.6%) and unexplained fever (0.6%). CONCLUSION: According to the results of current study, the use of unidirectional barbed suture without backward stitching appears to be safe for the vaginal cuff closure in TLH.