Bipedalism and the dawn of uterine fibroids.

The high prevalence and burden of uterine fibroids in women raises questions about the origin of these benign growths. Here, we propose that fibroids should be understood in the context of human evolution, specifically the advent of bipedal locomotion in the hominin lineage. Over the ≥7 million years since our arboreal ancestors left their trees, skeletal adaptations ensued, affecting the pelvis, limbs, hands, and feet. By 3.2 million years ago, our ancestors were fully bipedal. A key evolutionary advantage of bipedalism was the freedom to use hands to carry and prepare food and create and use tools which, in turn, led to further evolutionary changes such as brain enlargement (encephalization), including a dramatic increase in the size of the neocortex. Pelvic realignment resulted in narrowing and transformation of the birth canal from a simple cylinder to a convoluted structure with misaligned pelvic inlet, mid-pelvis, and pelvic outlet planes. Neonatal head circumference has increased, greatly complicating parturition in early and modern humans, up to and including our own species. To overcome the so-called obstetric dilemma provoked by bipedal locomotion and encephalization, various compensatory adaptations have occurred affecting human neonatal development. These include adaptations limiting neonatal size, namely altricial birth (delivery of infants at an early neurodevelopmental stage, relative to other primates) and mid-gestation skeletal growth deceleration. Another key adaptation was hyperplasia of the myometrium, specifically the neomyometrium (the outer two-thirds of the myometrium, corresponding to 90% of the uterine musculature), allowing the uterus to more forcefully push the baby through the pelvis during a lengthy parturition. We propose that this hyperplasia of smooth muscle tissue set the stage for highly prevalent uterine fibroids. These fibroids are therefore a consequence of the obstetric dilemma and, ultimately, of the evolution of bipedalism in our hominin ancestors.

Hysteroscopic Endometrial Resection in Women Treated With Tamoxifen for Breast Cancer Provides Definitive Diagnosis and Effective Long-Term Therapy.

We evaluated resectoscopic surgery for definitive diagnosis and long-term therapy in 16 symptomatic tamoxifen-treated women with breast cancer who presented with abnormal uterine bleeding and/or intrauterine anomalies. Seven pre-menopausal women had benign pre- and post-operative endometrial biopsy, and 4 had benign polyps. At a median of 7 years of follow-up (range 2-8 y), all remained amenorrheic. Of 9 post-menopausal women, pre-operative biopsy was inadequate in 4, benign endometrium was found in 4, and non-atypical endometrial hyperplasia was found in 1. Post-operatively, all had benign pathology, 8 having polyp and 1 leiomyoma. At a median follow-up of 7 years (range 2-13 y), all were amenorrheic, with no recurrence of breast cancer or uterine pathology.

Hysteroscopy and female infertility: a fresh look to a busy corner.

Hysteroscopy has evolved from the traditional art of examining the uterine cavity for diagnostic purposes to an invaluable modality to concomitantly diagnose and (see and) treat a multitude of intrauterine pathologies, especially in the field and clinics specialising in female reproduction. This article reviews the literature on the most common cervical, endometrial, uterine and tubal pathologies such as chronic endometritis, endometrial polyps, adenomyosis, endometriosis, endometrial atrophy, adhesions, endometrial hyperplasia, cancer, and uterine malformations. The aim is to determine the efficiency of hysteroscopy compared with other available techniques as a diagnostic and treatment tool and its association with the success of in vitro fertilisation procedures. Although hysteroscopy requires an experienced operator for optimal results and is still an invasive procedure, it has the unique advantage of combining great diagnostic and treatment opportunities before and after ART procedures. In conclusion, hysteroscopy should be recommended as a first-line procedure in all cases with female infertility, and a special effort should be made for its implementation in the development of new high-tech procedures for identification and treatment infertility-associated conditions.

Distension media delivery systems in hysteroscopy: past, present and future.

To examine the uterine cavity and/or to perform hysteroscopic surgery, one has to access the uterine cavity through the cervix, distend the cavity with a fluid (liquid or gas) to visualize it with a telescope and/or a camera system and use energy (mechanical or thermal) to affect and/or remove tissue. Distension of the uterine cavity then is an important component of hysteroscopy, and during the last century, numerous attempts have been made to achieve an undistorted and unobstructed panoramic view of the uterine cavity. In order to achieve this goal, the uterine cavity has been distended with fluids using a variety of techniques, including gravity-assisted systems, pressure cuffed systems, and electronic pumps. Excessive fluid intravasation during hysteroscopy can lead to significant complications, and hence, automated fluid delivery systems have been developed recently to provide a safe and more efficient method of fluid delivery. This review aims to describe the evolution of distension media delivery systems chronologically from the 1900s to the present day.

Diagnosis of Endometriosis at Laparoscopy: A Validation Study Comparing Surgeon Visualization with Histologic Findings.

OBJECTIVE: This study aimed to evaluate the validity of laparoscopic visualization for the diagnosis of endometriosis compared with histopathology. METHODS: We conducted a retrospective chart review at a tertiary care hospital in Canada for the period of April 1, 2016 to March 31, 2017. Of 1069 women, 96 were selected for having undergone laparoscopic visualization and concurrent histopathological biopsy for suspected endometriosis. Standard measures of validity for diagnostic tests (sensitivity, specificity, positive predictive and negative predictive values, accuracy) were used. RESULTS: Mean age of the 96 women included was 40 ± 7.2 years, and median gravidity and parity were 1 (IQR 0-3) and 0 (IQR 0-2), respectively. Common symptoms were abdominal and pelvic pain (41.7%), menstrual bleeding concerns (34.4%), dysmenorrhea (29.2%), and infertility (8.3%). Approximately one-third of women had endometriomas (31.3%), while more than half had deep infiltrating endometriosis (59.4%). The diagnosis of endometriosis was made by surgeons at laparoscopic visualization in 82.3% of women and by histopathology in 74.0%. Using histopathology as the gold standard, sensitivity for laparoscopic visualization was 90.1% (95% CI 81.0-95.1), while specificity was 40.0% (95% CI 23.4-59.3). Positive and negative predictive values were 81.0% (95% CI 71.0-88.1) and 58.8% (95% CI 36.0-78.4), respectively; and the accuracy was 77.1% (95% CI 67.7-84.4). CONCLUSION: Although laparoscopic visualization had relatively high sensitivity and positive predictive value, its specificity and negative predictive value were relatively low. These findings support the use of laparoscopic visualization with histopathological analysis for accurate diagnosis of endometriosis.

Impact of the COVID-19 Pandemic on Access to Fertility Care: A Retrospective Study at a University-Affiliated Fertility Practice.

OBJECTIVE: To elucidate the impact of the COVID-19 pandemic on access to fertility services. METHODS: A retrospective quality improvement study was conducted at a university-affiliated fertility practice in southwestern Ontario. Annual procedural volumes for intrauterine and donor inseminations (IUI/DI), in vitro fertilization and intracytoplasmic sperm injections (IVF/ICSI), and frozen embryo transfers (FET) during the COVID-19-affected year were compared with mean annual volumes from the 2 preceding years. In addition, volumes for the same procedures were compared between the first quarter of 2021 and mean first quarter volumes from 2018 to 2019. Piecewise linear regressions were conducted to evaluate whether any changes in monthly procedural volume were attributable to the COVID-19 pandemic. RESULTS: In 2020, our fertility practice attained the mean annual volumes of 89.7% for IUI/DI, 69.0% for IVF/ICSI, and 60.6% for FET. In contrast, in 2021, we performed mean first quarter volumes of 130.1% for IUI/DI, 164.3% for IVF/ICSI, and 126.8% for FET. The slopes of the pre- and post-COVID-19 segments of the piecewise linear regressions were significantly different for IUI/DI (P < 0.001) and IVF/ICSI (P = 0.001), but not for FET (P = 0.133). CONCLUSION: The COVID-19 pandemic resulted in decreased annual volumes of medically assisted reproductive procedures at a university-affiliated fertility practice in southwestern Ontario. Impact on monthly procedural volume was confirmed for IUI/DI and IVF/ICSI by linear regression. Local adaptations helped compensate and exceed expected volumes in 2021. As a result, the COVID-19 pandemic resulted in a short-lived limitation in access to fertility care.

Uterine kisspeptin receptor critically regulates epithelial estrogen receptor α transcriptional activity at the time of embryo implantation in a mouse model.

Embryo implantation failure is a major cause of infertility in women of reproductive age and a better understanding of uterine factors that regulate implantation is required for developing effective treatments for female infertility. This study investigated the role of the uterine kisspeptin receptor (KISS1R) in the molecular regulation of implantation in a mouse model. To conduct this study, a conditional uterine knockout (KO) of Kiss1r was created using the Pgr-Cre (progesterone receptor-CRE recombinase) driver. Reproductive profiling revealed that while KO females exhibited normal ovarian function and mated successfully to stud males, they exhibited significantly fewer implantation sites, reduced litter size and increased neonatal mortality demonstrating that uterine KISS1R is required for embryo implantation and a healthy pregnancy. Strikingly, in the uterus of Kiss1r KO mice on day 4 (D4) of pregnancy, the day of embryo implantation, KO females exhibited aberrantly elevated epithelial ERα (estrogen receptor α) transcriptional activity. This led to the temporal misexpression of several epithelial genes [Cftr (Cystic fibrosis transmembrane conductance regulator), Aqp5 (aquaporin 5), Aqp8 (aquaporin 8) and Cldn7 (claudin 7)] that mediate luminal fluid secretion and luminal opening. As a result, on D4 of pregnancy, the lumen remained open disrupting the final acquisition of endometrial receptivity and likely accounting for the reduction in implantation events. Our data clearly show that uterine KISS1R negatively regulates ERα signaling at the time of implantation, in part by inhibiting ERα overexpression and preventing detrimentally high ERα activity. To date, there are no reports on the regulation of ERα by KISS1R; therefore, this study has uncovered an important and powerful regulator of uterine ERα during early pregnancy.

In vitro fertilization cycles stimulated with follitropin delta result in similar embryo development and quality when compared with cycles stimulated with follitropin alfa or follitropin beta.

OBJECTIVE: To study the impact of follitropin delta for ovarian stimulation on embryo development and quality compared with that of follitropin alfa or beta in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated, hospital-based fertility clinic. PATIENTS: A total of 403 IVF/ICSI cycles were conducted from September 1, 2018 to December 31, 2019. Cycles were grouped on the basis of stimulation with follitropin delta vs. follitropin alfa or beta. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Embryo parameters and clinical pregnancy and implantation rates. RESULTS: Ovarian stimulation using follitropin delta resulted in no statistically significant difference in day 3 embryo quality between the control group and follitropin delta group (median 0.50 vs. 0.54 for good quality embryos and median 0.25 vs. 0.20 for intermediate quality embryos). Although on initial analysis there was a lower proportion of good quality blastocysts in the follitropin delta group than in the control group (0.11 vs. 0.22), this difference was no longer present when day 3 after fertilization vitrification and transfer cycles were excluded (0.26 vs. 0.33 follitropin delta vs. control). The clinical pregnancy rates and clinical implantation rates were similar in both groups in fresh transfer cycles. CONCLUSIONS: Stimulation with follitropin delta in IVF/ICSI cycles resulted in similar embryo development and pregnancy rates compared with those of stimulation with follitropin alfa or beta.

Complication Rates after Endometrial Ablation in Ontario: A Cohort Analysis of 76 446 Patients.

STUDY OBJECTIVES: Endometrial ablation (EA) is an alternative to hysterectomy for the management of heavy menstrual bleeding; however, EA is not without risk. Our objective was to determine complication rates in women undergoing EA in the province of Ontario over a 15-year time period. The primary outcome was a composite of multiple complications within 30 to 180 days of surgery. The secondary outcomes included mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. DESIGN: Retrospective cohort study using Cochran-Armitage test for trend. SETTING: Administrative data from the Canadian province of Ontario, assessing patients undergoing surgery in a publicly funded healthcare system. PATIENTS: Women in Ontario undergoing a primary EA over a 15-year time period. INTERVENTIONS: The intervention was a primary EA. MEASUREMENTS AND MAIN RESULTS: We assessed for genitourinary complication, fistula, gastrointestinal complication, pain, control of bleeding, blood transfusion, infectious complication, venous thromboembolism, fluid overload, thermal injury, and other injuries related to surgery. The secondary outcomes included 1-month and 6-month mortality, length of hospital stay, hospital readmission, and emergency department visit within 30 days of discharge. A total of 76 446 primary EAs were evaluated from 2002 to 2017, with the number of EAs per year increasing over the study period by 47%. Complications were seen in 4.8% of the cohort, with the complication rate being relatively stable over time. Although 6.2% of the cohort re-presented to the emergency department, <1% required readmission, and <0.05% died within 180 days. On multivariable analysis, the risk of complications increased with a preoperative diagnosis of other than bleeding (odds ratio [OR] 2.89; 95% confidence interval [CI], 2.61-3.21; p <.001), previous abdominal surgery (OR 1.42; 95% CI, 1.28-1.56; p <.001), and American Society of Anesthesiologists score 3+ (OR 1.37; 95% CI, 1.27-1.48; p <.001). CONCLUSION: Primary EA is associated with complications in <5% of the patients, with serious complications infrequent.

Classification systems of Asherman's syndrome. An old problem with new directions.

Intrauterine adhesion (IUA) formation and the resulting Asherman's syndrome (AS) is an unfortunate clinical condition that occurs when the endometrium is damaged as a consequence of trauma, such as vigorous curettage, infection, or some Müllerian anomaly. The most frequent symptoms include hypo/amenorrhea, infertility, and adverse reproductive outcomes. Prevention of IUA formation is essential; however, when present, accurate diagnosis and surgical intervention (hysteroscopic adhesiolysis) are required. The outcome of this treatment is based on the technique and the extent of surgery performed which depends on the severity and complexity of the disease. Hence its classification becomes particularly important to determine a standardized therapy for each case and patient counseling regarding the prognosis. In this article, we aim to describe the IUAs classification systems that have been proposed comparing the merits and demerits of each one.

Guideline No. 412: Laparoscopic Entry for Gynaecological Surgery.

OBJECTIVE: To evaluate the benefits and risks of laparoscopic surgery and provide clinical direction on entry techniques, technologies, and their associated complications in gynaecological surgery. TARGET POPULATION: All patients, including pregnant women and women with obesity, undergoing laparoscopic surgery for various gynaecological indications. OPTIONS: The laparoscopic entry techniques and technologies reviewed in formulating this guideline included the closed (Veress needle-pneumoperitoneum-trocar) technique, direct trocar insertion, open (Hasson) technique, visual entry systems, and disposable shielded and radially expanding trocars. OUTCOMES: Implementation of this guideline should optimize decision-making in the selection of entry technique for laparoscopic surgery. EVIDENCE: We searched English-language articles from September 2005 to December 2019 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library using the following MeSH search terms alone or in combination: laparoscopic entry, laparoscopy access, pneumoperitoneum, Veress needle, open (Hasson), direct trocar, visual entry, shielded trocars, radially expanded trocars, and laparoscopic complications. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Canadian Task Force on Preventive Health Care approach (Appendix A). INTENDED AUDIENCE: Surgeons performing laparoscopic gynaecological surgery. SUMMARY STATEMENTS: RECOMMENDATIONS.

Reproductive outcomes of infertile women undergoing "see and treat" office hysteroscopy: a retrospective observational study.

INTRODUCTION: This study aimed to assess the feasibility and efficacy of office hysteroscopy to diagnose and treat the specific uterine pathologies frequently diagnosed and thought to be associated with female infertility. MATERIAL AND METHODS: Using office hysteroscopy, we examined the uterine cavity in women with primary or secondary infertility and evaluated the reproductive outcomes of those affected by one or more pathologies, including cervico-isthmic adhesions, intrauterine polyps and intrauterine adhesions. Additional patient characteristics considered were age and parity, uterine pathology, pain during hysteroscopy, and outcomes including spontaneous pregnancies achieved and time between treatment and pregnancy. RESULTS: Reproductive outcomes of 200 patients affected by one or more uterine pathologies were evaluated. Cervico-isthmic adhesions were the most frequent findings in older women, with nearly 80% of them achieving pregnancy sooner than the others in our study. Spontaneous pregnancy rates following office hysteroscopy were 76%, 53% and 22% in women with cervico-isthmic adhesions, polyps (< 5 mm) and intrauterine adhesions, respectively. CONCLUSIONS: Office hysteroscopy is a feasible and highly effective diagnostic and therapeutic procedure for cervico-isthmic and intrauterine adhesions, as well as for small polyps, allowing the resolution of female infertility related to these pathologies, without trauma and with only minimal discomfort.