Fertility and Sterility

Solving the mysteries surrounding uterine fibroids: are we almost there?

A better understanding of uterine fibroid-related pathogenesis and symptoms like uterine bleeding and infertility is mandatory.

A prospective study of hair dyes and uterine leiomyomata incidence in the study of environment, lifestyle, and fibroids

To investigate associations between hair dye use and incident uterine leiomyomata (fibroids) among Black participants from the Study of Environment, Lifestyle, and Fibroids. Prospective cohort study. Reproductive-aged (26-39 years) individuals with an intact uterus residing in the Detroit, Michigan area (n = 868). Self-reported hair dye use (any use vs. no use) in the previous 12 months queried on structured questionnaires. Fibroid incidence assessed by transvaginal ultrasounds. We fit Cox proportional hazard models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for age, time in study, educational attainment, annual household income, occupational status, body mass index, age at menarche, parity, use of progestin-only injectable contraceptives within the past 2 years, alcohol consumption, and smoking status. One hundred and forty nine incident fibroid cases were identified over 3,458 person-years of follow-up. After adjustment for confounders, use of any hair dye product (HR = 1.44; 95% CI = 0.91, 2.26) and rinses that fade (HR = 1.98; 95% CI = 1.04, 3.79) in the previous 12 months was associated with increased fibroid risk, compared with no use, although associations were generally imprecise. In this cohort, use of hair dye products was modestly associated with a higher fibroid risk, which has important public health implications.

Clinical signs and diagnosis of fibroids from adolescence to menopause

The aim of this review was to provide an updated assessment of the present diagnostic tools and clinical symptoms and signs to evaluate uterine fibroids (UFs) on the basis of current guidelines, recent scientific evidence, and a PubMed and Google Scholar search for peer-reviewed original and review articles related to clinical signs and diagnosis of UFs. Approximately 50%-75% of UFs are considered nonclinically relevant. When present, the most common symptoms are abnormal uterine bleeding, pelvic pain and/or bulk symptoms, and reproductive failure. Transvaginal ultrasound is recommended as the initial diagnostic modality because of its accessibility and high sensitivity, although magnetic resonance imaging appears to be the most accurate diagnostic tool to date in certain cases. Other emerging techniques, such as saline infusion sonohysterography, elastography, and contrast-enhanced ultrasonography, may contribute to improving diagnostic accuracy in selected cases. Moreover, artificial intelligence has begun to demonstrate its ability as a complementary tool to improve the efficiency of UF diagnosis. Therefore, it is critical to standardize descriptions of transvaginal ultrasound images according to updated classifications and to individualize the use of the different complementary diagnostic tools available to achieve precise uterine mapping that can lead to targeted therapeutic approaches according to the clinical context of each patient.

Fertility preservation for women with borderline ovarian tumors: fertility-sparing surgery

Reproductive and obstetrical outcomes with the overall survival of fertile-age women treated with fertility-sparing surgery for borderline ovarian tumors in Sweden: a prospective nationwide population-based study

To assess the efficacy of fertility-sparing surgery (FSS) in terms of reproductive outcomes by following FSS for borderline ovarian tumors (BOTs) and comparing the safety of FSS versus radical surgery (RS). Nationwide cohort study based on prospectively recorded data. Sweden. All women of reproductive age (18-40 years) treated in Sweden for stage I BOT with the use of FSS or RS from 2008 to 2015, identified in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). FSS or RS. Reproductive outcomes: natural conception, use of assisted reproductive technology (ART), live birth and obstetrical outcomes. Safety outcome: overall survival (OS) rates, comparing women undergoing FSS versus RS. The FSS cohort was linked to the Swedish Medical Birth Register to identify all women who had given birth after FSS and to obtain detailed obstetrical data. For information on ART treatment, the National Quality Registry for Assisted Reproduction was consulted. OS rate comparisons were conducted by means of Kaplan-Meier estimates. Of the 277 women with BOTs, 213 (77%) underwent FSS, 183 (86%) unilateral salpingo-oophorectomy, and 30 (14%) cystectomy. Following FSS, 50 women gave birth to 62 healthy children, 8% of which were preterm. Only 20 (9%) of the women underwent ART treatment. OS was similar in women treated with FSS and RS. Natural fertility was maintained after FSS; only 9% required ART treatment. FSS was also deemed to be equivalent to RS regarding survival outcome.

Perioperative outcomes in a nationwide sample of patients undergoing surgical treatment of ovarian endometriomas

To evaluate the perioperative outcomes of premenopausal women undergoing cystectomy or oophorectomy for ovarian endometriomas (OMAs) and other benign neoplasms. Retrospective cohort study. Clinical database containing information from 580 US hospitals. Women 18 to 50 years old who underwent ovarian cystectomy or oophorectomy for benign indications between 2010 and 2020. We compared procedure route, length of hospital stay, and complication rates by surgical indication (OMA vs. other benign neoplasms) and surgical procedure (cystectomy vs. oophorectomy). Thirty-day perioperative adverse events following adnexal surgery, including conversion to laparotomy, blood transfusion, ileus, urinary tract injury, bowel injury, readmission, and death. We identified 120,208 ovarian cystectomies (28,182 OMAs and 92,026 other indications) and 53,476 oophorectomies (8,622 OMAs and 44,854 other indications). During cystectomy, patients with OMAs more commonly experienced conversion to laparotomy (5.1% vs. 3.1%) and readmission (8.5% vs. 7.1%). For oophorectomies, patients with OMAs less frequently had minimally invasive surgery (55.8% vs. 64.8%) or outpatient procedures (33.8% vs. 41.8%). Urinary tract and bowel injuries were rare. Multivariable logistic regression demonstrated that the presence of OMA predicted composite complications during cystectomy (adjusted odds ratio [aOR] 1.23, 95% confidence interval [CI] 1.18-1.28) but not during oophorectomy (aOR 1.05, 95% CI 0.99-1.12). Patients with OMAs had 1.37 times the odds of a composite complication during oophorectomy than during cystectomy (95% CI 1.28-1.47). Patients undergoing ovarian cystectomy for OMAs had higher rates of perioperative adverse events than patients undergoing ovarian cystectomy for other benign neoplasms. Laparotomies were performed more often during oophorectomies for OMAs than for other benign indications.

How sparing is fertility-sparing surgery for early-stage cervical cancer?

The validity of the subsequent pregnancy index score for fertility-sparing trachelectomy in early-stage cervical cancer

To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy. Retrospective cohort. Academic multicenter. Women ages <45 years with clinical stage I-II cervical cancer were enrolled between 2009 and 2013 (n = 393). Planned fertility-sparing trachelectomy. Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined. There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%). The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.

Linzagolix rapidly reduces heavy menstrual bleeding in women with uterine fibroids: an analysis of the PRIMROSE 1 and 2 trials

To study the timing of the effect of linzagolix, an oral gonadotropin-releasing hormone receptor antagonist, on significant reduction in heavy menstrual bleeding (HMB) in women with uterine fibroids. The study used pooled data from PRIMROSE 1 and PRIMROSE 2, two double-blind, similar placebo-controlled trials of linzagolix in the United States and Europe, respectively. Eligible participants were randomized equally across four treatment arms (linzagolix 100 mg and 200 mg, with and without concomitant hormonal add-back therapy [ABT] consisting of 1-mg estradiol and 0.5-mg norethisterone acetate) and one placebo arm. The cumulative incidence of achieving clinically significant HMB reduction and maintaining it to week 24 was compared between the linzagolix arms and the placebo arm using the Kaplan-Meier plots adjusted for confounding by race and study (PRIMROSE 1 vs. PRIMROSE 2). The PRIMROSE trials randomized 1,012 women aged ≥18 years with ultrasound-confirmed uterine fibroids and HMB. Linzagolix (100 mg and 200 mg, with and without hormonal ABT) vs. placebo. The main outcome of this analysis was the time to achievement of clinically significant HMB reduction and its maintenance up to week 24. The onset of action in achieving and maintaining clinically significant HMB reduction was significantly more rapid for the linzagolix treatment arms than for the placebo arm, with a median time of <4 weeks for most linzagolix doses (except 100 mg alone). The fastest onset was seen with linzagolix 200 mg with or without ABT doses, with a median time of only 3 days. The cumulative incidence of achieving clinically significant HMB reduction by week 4 and maintaining it to week 24 was also significantly higher for the linzagolix treatment arms than for the placebo arm. Specifically, across four linzagolix treatment arms, 23.2%-68.1% achieved clinically significant HMB reduction by week 4 and maintained it to week 24 vs. 7.8% for the placebo arm. Linzagolix was associated with a quick effect on reducing clinically significant HMB compared with placebo. Linzagolix, thus, offers a novel noninvasive treatment approach for the rapid management of HMB symptoms in patients with uterine fibroids.

Linzagolix with and without hormonal add-back therapy for symptomatic uterine fibroids: PRIMROSE 1 &amp; 2 long-term extension and withdrawal study

To evaluate whether oral linzagolix administered once daily for up to 52 weeks (extension study) at a dose of 100 mg or 200 mg with or without hormonal add-back therapy (ABT) (1.0 mg estradiol; 0.5 mg norethisterone acetate) can maintain the efficacy and tolerability seen at 6 months of therapy and whether there is any recurrence of symptoms (bleeding and pain) after cessation of therapy (withdrawal study). PRIMROSE 1 and PRIMROSE 2 were essentially identical, randomized, parallel, double-blind, and placebo-controlled phase 3 trials conducted in women with uterine fibroid-associated heavy menstrual bleeding (HMB) (menstrual blood loss [MBL] of more than 80 mL per cycle over 2 menstrual cycles). In PRIMROSE 1 and 2, 1,012 women were included in the full analysis set. Eligible subjects were women aged 18 years or older with ultrasound-confirmed fibroids and HMB of at least 80 mL blood loss per cycle for a minimum of two cycles, as determined by the alkaline hematin method. Eligible participants had to have at least one fibroid measuring 2 cm in diameter or more (or multiple small fibroids with overall uterine volume exceeding 200 cm Eligible women with uterine fibroid-associated HMB were randomly assigned at a 1:1:1:1:1 ratio to one of five masked daily treatment: placebo, 100 mg linzagolix alone, 100 mg linzagolix with hormonal ABT (1 mg estradiol and 0.5 mg norethisterone acetate), 200 mg linzagolix alone , or 200 mg linzagolix with hormonal ABT (1 mg estradiol and 0.5 mg norethisterone acetate). After 24 weeks, patients assigned to the placebo or 200 mg linzagolix alone groups were switched to 200 mg linzagolix with ABT, except in PRIMROSE 1, in which 50% of subjects on a placebo continued with the placebo (random selection) until week 52. All other women continued on the original study medication. Efficacy and safety were evaluated at week 52 (extension study) as well as week 64 (withdrawal study). Bone mineral density was also assessed at week 76 (6 months after cessation of therapy). The primary endpoint was decreased MBL to less than 80 mL and a reduction of more than 50% from baseline. Specifically, this study sought to determine whether the reduction in MBL and other secondary outcomes, such as uterine volume and pain, observed at 24 weeks could be maintained over an extended (52 weeks) treatment period and further withdrawal period. In the pooled data from PRIMROSE 1 and PRIMROSE 2 extension studies, the significantly higher proportion of women showing a reduction in HMB in all linzagolix (with or without ABT) treatment groups observed at week 24, was maintained until week 52. Percentages of women with reduced MBL at week 52 (based on the pooled week 52 full analysis set) were 55.0% in the 100 mg group, 86.1% in the 100 mg with ABT group, 76.7% in the 200 mg group/200 mg with ABT, and 89.9% in the 200 mg with ABT group. Of subjects previously treated with linzagolix and in amenorrhea by week 52, 88.8% reported their first bleed or heavy bleeding between weeks 52 and 64. In both PRIMROSE studies, the most common adverse events up to week 52 were hot flushes. Their incidence had returned to baseline values by week 64. Bone mineral density was well preserved in all groups at week 52. In women treated with 200 mg linzagolix alone up to week 24, initial bone mineral density loss (lumbar spine) recovered by week 52 after adding ABT from week 24 onwards. Findings at 52 weeks confirmed the benefits of treatment observed at 24 weeks. At 52 weeks, linzagolix 100 mg or 200 mg with or without ABT was found to reduce HMB, which is a burden for women with uterine fibroids. Their quality of life was improved. Risks of bone loss and vasomotor symptoms were minimized as a result of ABT administration. Partial suppression with once-daily linzagolix 100 mg without ABT potentially provides a unique option for chronic treatment of symptomatic uterine fibroids in women who do not wish to have ABT or in whom it is contraindicated. The relatively fast recurrence of uterine fibroid-associated symptoms after cessation of therapy is an argument in favor of long-term continuation of treatment. PRIMROSE1 (NCT03070899) PRIMROSE 2 (NCT03070951).

Long-term safety of controlled ovarian stimulation for fertility preservation before chemotherapy treatment in patients with breast cancer

The modern management of uterine fibroids-related abnormal uterine bleeding

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

Childhood adversity and risk of endometriosis, fibroids, and polycystic ovary syndrome: a systematic review

Although childhood adversity has been extensively studied in relation to various health outcomes, investigation of its association with gynecological conditions remains limited. To systematically review studies examining the effect of childhood adversity on the prevalence of three gynecological conditions: endometriosis; fibroids; and polycystic ovary syndrome (PCOS) in the population. Six databases were searched from inception to March 12, 2024. Observational studies of women with exposure to adversity before the age of 18 and an outcome of endometriosis, fibroids, and/or PCOS were eligible for inclusion. Studies were summarized through a qualitative synthesis. We evaluated the risk of bias using the Newcastle-Ottawa Scale. Seven studies that reported on the association between a form of childhood adversity and endometriosis, fibroids, and or PCOS were selected for review. All seven studies received a moderate risk of bias score. Cumulative exposure to childhood adversity was associated with an increased risk of endometriosis and fibroids. Childhood exposure to sexual abuse was associated with an increased risk of endometriosis and fibroids. Exposure to physical abuse in childhood was associated with a greater risk of fibroids. A small number of studies have shown an association between childhood adversity and the development of endometriosis and fibroids in later life. These initial findings warrant further investigation in larger studies using standardized measures.

Combined removal of ovarian teratoma and oocyte retrieval by laparoscopic surgery under regional anesthesia

To describe the simultaneous laparoscopic approach for teratoma removal and oocyte retrieval performed under regional anesthesia in a woman, desiring to preserve fertility. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites, and other applicable sites. Video case report demonstrating the clinical management and laparoscopic teratoma removal combined with oocyte retrieval accomplished under regional anesthesia. We present a case of a 31-year-old woman who referred to our Fertility Center with a previous history of right salpingo-oophorectomy for mucinous ovarian cystadenoma and the presence of a large ovarian teratoma of ten centimeters of the contralateral ovary. The ovarian stimulation started in the early follicular phase. Not being able to visualize follicular growth during the ovarian stimulation, it was decided to adopt fixed protocol with antagonist on the 5th day and to proceed, on 15th day, with a laparoscopic pick-up and simultaneous removal of the cyst. Laparoscopic surgery was performed: the left ovary appeared larger in size for the presence of the suspicious mature dermoid cyst and multiple follicles, previously not identified at ultrasound imaging. The follicles contained oocytes that were aspirated with an aspiration needle of 17 G connected to a craft suction pump. Then, practicing the stripping technique, an enucleation of the ovarian cyst was performed. Surprisingly, the removal of the cyst revealed other follicles that were readily aspirated. The patient remained awake during the entire procedure and a low pressure of 10 mmHg was maintained at 15° of Trendelenburg position. A total of seven follicles were aspirated, seven oocytes were retrieved, and six mature oocytes were cryopreserved. The cyst was totally removed and no intracavitary spillage was caused. Simultaneous laparoscopic approach for teratoma removal and oocyte cryopreservation should be considered an effective fertility preservation strategy in patients in whom the presence of an ovarian neoformation does not allow visualization of growing follicles by ultrasound. Laparoscopic oocyte retrieval under regional anesthesia is a safe and well-tolerated technique and should be considered for patients where the transvaginal approach could not be performed.

Ovarian tissue cryopreservation in pediatric patients with malignancy involving the ovary

Robotic-assisted uterine transposition followed by anatomic pelvic repositioning for a patient with intramural fibroids and rectal cancer

To report the first described case of robotic-assisted utero-ovarian transposition followed by anatomic repositioning in the pelvis and cervicovaginal anastomosis in a woman with uterine fibroids, which was performed for fertility preservation in the context of pelvic radiation for rectal cancer. Description of technique and live-action narrated surgical footage showing uterine transposition and repositioning. University hospital. A 36-year-old woman with a new diagnosis of cT3N2M0 rectal adenocarcinoma planned for neoadjuvant chemotherapy and pelvic radiation and desired fertility preservation permissive of future pregnancy. A transvaginal ultrasound revealed a 5-cm posterior leiomyoma and a normal endometrial cavity. The patient elected for utero-ovarian transposition before chemoradiation. The patient included in this video gave consent for publication and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites. Per institutional guidelines, an Institutional Review Board review was not required. Robotic-assisted utero-ovarian transposition was performed in an inpatient setting 2 weeks after ovarian stimulation and oocyte retrieval. She was given a gonadotropin-releasing hormone agonist for menstrual suppression after oocyte retrieval. The uterus and adnexa were transposed en bloc to the upper abdomen, with perfusion via retroflected infundibulopelvic ligaments. Intravenous indocyanine green was administered intraoperatively to visualize uterine perfusion. Three weeks postoperatively, the patient underwent surgical management of small bowel obstruction, which was successfully managed with laparoscopic adhesiolysis. The patient subsequently completed chemoradiation and had a complete response to the rectal tumor. She therefore elected for surveillance. Seven months after transposition and 2 months after completion of treatment, the patient underwent uncomplicated robotic-assisted utero-ovarian anatomic repositioning in the pelvis with cervicovaginal anastomosis. Chromopertubation confirmed tubal patency. Restoration of normal pelvic anatomy and resumption of reproductive physiology. At her 4-month postoperative visit, the cervix and vagina were normal in appearance. The patient reported the return of spontaneous menses and sexual activity without complications. This case is unique because of the presence of bulky intramural uterine fibroids. The described technique may be useful for selected cancer patients who desire to carry a pregnancy after pelvic radiation for cancer treatment, and demonstrates that patients considering utero-ovarian transposition need not be excluded solely on the basis of the presence of uterine fibroids.

Pathogenesis of uterine fibroids: current understanding and future directions

Fibroids are benign uterine tumors characterized by the proliferation of uterine smooth muscle cells, embedded in an abundant extracellular matrix. Their prevalence is estimated to be >50% in women aged >45 years. Fibroids represent a considerable health burden. It is time to acquire a deeper mechanistic understanding of uterine fibroid-related etiology and pathogenesis, which may help pinpoint new strategies and an individualized approach. There is a need to gather prospective data and conduct studies to compare alternative approaches and assess long-term outcomes with respect to quality of life, recurrence of symptoms (bleeding and bulk symptoms), fertility, and even complications The goal of this review was to evaluate the widely accepted pathogenesis and identify risks factors and future directions for clinical and basic research into fibroids.

Laparoscopic transfundal approach to cervical dilation: a novel treatment for cervical stenosis and cervical factor infertility

To demonstrate a novel technique used to restore cervical patency in a patient with severe iatrogenic cervical stenosis. Surgical video case report. A single academic institution. We highlight the case of a 35-year-old nulliparous woman with a history of primary infertility. Her past medical history was significant for focal, invasive, well-differentiated squamous cell carcinoma of the cervix, for which she underwent a loop electrosurgical excision procedure. During her infertility assessment, she was found to have an extremely stenotic cervix that was refractory to conventional treatment options. This video highlights our innovative laparoscopic transfundal technique used to restore her cervical patency. None, as this is a descriptive case report. Postoperatively, the patient had continued cervical patency for >1 year with successful fertility treatment resulting in pregnancy. To our knowledge, this is the first case report describing a laparoscopic transfundal approach used to reestablish cervical patency. This approach may be considered for patients with cervical stenosis who have not responded to standard conservative therapies.

First pregnancy and live birth from ex vivo-retrieved metaphase II oocytes from a woman with bilateral ovarian carcinoma: a case report

To report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo-retrieved mature oocytes from a woman with bilateral ovarian carcinoma. Case report. Fertility clinic. A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy of 96.1% according to International Ovarian Tumor Analysis Group recommendations for adnexal tumors, who desired fertility preservation before definitive surgical treatment. Cryopreservation of ex vivo-retrieved mature metaphase II oocytes is followed by fertilization with donor sperm and embryo transfer to a gestational carrier. Fertility preservation. After controlled ovarian stimulation, 12 metaphase II oocytes were retrieved from oophorectomized specimens and vitrified. Intracytoplasmic sperm injection with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, 2 of which were transferred to a gestational carrier, resulting in a normal, healthy singleton pregnancy, and the live birth of a healthy infant. Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies.

Association of platinum-based chemotherapy with live birth and infertility in female survivors of adolescent and young adult cancer

To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. Retrospective cohort study. US administrative database. We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. Platinum-based chemotherapy. We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively. Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.

Opportunistic salpingectomy at cesarean delivery: Is it a worthy choice?

Complications after opportunistic salpingectomy compared with tubal ligation at cesarean section: a retrospective cohort study

To compare perioperative and postoperative complications in patients who underwent opportunistic salpingectomy (OS) (removal of the fallopian tubes for ovarian cancer risk reduction during another surgery) at the time of cesarean section (C-section) with those in patients who underwent tubal ligation. A population-based, retrospective cohort study. British Columbia, Canada. A total of 18,184 patients were included in this study, of whom 8,440 and 9,744 underwent OS and tubal ligation, respectively. Patients who underwent OS during a C-section were compared with those who underwent tubal ligation during a C-section. We examined the perioperative outcomes, including operating room time, length of hospital stay, surgical complications such as infections, anemia, incision complications, injury to a pelvic organ, or operating room return; postoperative complications, including physician visits for a postoperative infection or visits that resulted in ultrasound or laboratory examinations and hospital readmissions in the 6 weeks after discharge; and likelihood to fill a prescription for antibiotics or analgesics. The OS group had decreased odds of perioperative complications compared with the tubal ligation group (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.61-0.99). Patients who underwent OS did not have increased risks of physician visits for surgical complications, such as infection, or hospital readmissions in the 6 weeks after hospital discharge. In addition, these patients had 18% and 23% increased odds of filling prescriptions for nonsteroidal anti-inflammatory drugs (aOR, 1.18; 95% CI, 1.07-1.28) and opioids (aOR, 1.23%; 95% CI, 1.12-1.35), respectively. In this population-based, real-world study of OS at C-section, we report decreased perioperative complications and no difference in postoperative complications between patients who underwent OS and those who underwent tubal ligation. Patients who underwent OS had an increased likelihood of filling a prescription for nonsteroidal anti-inflammatory drugs and opioids in the 6 weeks after hospital discharge. This result should be interpreted with caution because we did not have data on over-the-counter medication use and, thus, not all prescription analgesics were captured in our data. Our data suggest that OS after C-section is a safe way to provide effective contraception and ovarian cancer risk reduction.

vNOTES retroperitoneal transient uterine artery occlusion: a new approach to control bleeding during a high-risk evacuation of products of conception

To describe a retroperitoneal transient occlusion of the uterine or internal iliac artery in conjunction with a high-risk evacuation of products of conception. The procedure was performed vaginally, minimally invasively, via vaginal natural orifice transluminal endoscopic surgery. Description of the surgical technique using original video footage. This study was exempted from requiring hospital institutional review board approval. Teaching hospital. A 34-year-old woman (G8P3) with a medical history of 2 cesarean sections, 1 partial mole, and a missed abortion with 2.8 L of blood loss. The patient presented after 10 weeks of amenorrhea. Ultrasound revealed a large blood-filled niche in the cesarean section scar with a thin overlying myometrium. A partial mole was suspected as well as increased vascularization in the myometrium and enhanced myometrial vascularity with arterial flow velocities of 100 cm/s. A risk of heavy blood loss in conjunction with curettage was anticipated. The patient had a strong preference for a fertility-preserving treatment, and after informed consent, she opted for transient occlusion of the uterine arteries with subsequent suction evacuation of the molar pregnancy. The patient signed a consent form accepting the procedure. The patient included in this video provided consent for publication of the video and posting of the video online including social media, the journal website, and scientific literature websites. Institutional review board approval was not required in accordance with the IDEAL guidelines. A vaginal incision was made over the bladder, and the vaginal mucosa was dissected. The paravesical space was dissected over the arcus tendinous, and the pelvic retroperitoneal space was opened. A small (7 cm) GelPOINT V-Path (Applied Medical, Rancho Santa Margarita, California) was inserted into the obturator fossa and insufflated with 10 CO Not applicable. The patient recovered swiftly without complications. Pathology confirmed a partial molar pregnancy. Uterine or internal iliac artery ligation can be lifesaving in situations with massive bleeding from the uterus. Current minimally invasive approaches are laparoscopic vessel ligation and, more commonly, uterine artery embolization, which has unclear impact on fertility and has shown an increased risk of intrauterine growth restriction, miscarriage, and prematurity. As the patient was undergoing a vaginal evacuation of pregnancy, a vaginal and retroperitoneal approach of artery ligation was deemed least invasive. In patients with fertility-preserving wishes, care should to be taken to avoid as much trauma as possible to the endometrium. Optimized blood control, and a shorter duration of using a curette, may potentially reduce the risk of endometrial damage. We present a novel minimally invasive approach via vaginal natural orifice transluminal endoscopic surgery-retroperitoneal transient occlusion of the internal iliac or uterine artery. The whole procedure can be performed by the operating gynecologist, and the occlusion is transient and can be reversed in a stepwise controlled manner.

Reply of the authors: comment on “Risk of hysterectomy at the time of myomectomy - An underestimated surgical risk”

Transforming traditional treatment of retained productions of conception: Is it time to embrace hysteroscopic morcellation as a first-line treatment?

Mini-laparotomy myomectomy and the art of refinement

Exploring the feasibility of anti-PD-1/PD-L1 immunotherapy in endometriosis-associated ovarian cancer

Infiltrating T lymphocytes and programmed cell death protein-1/programmed death-ligand 1 expression in endometriosis-associated ovarian cancer

To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE). Case-control, retrospective study. Research University Hospital. A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives. Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1. To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases. Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile. Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.

Endometriosis presenting as vaginal polyps: outpatient vaginoscopic treatment

To demonstrate an outpatient vaginoscopic technique for treating multiple vaginal polyps. Demonstration of surgical technique using slides, pictures, and video. Private hospital. Thirty-two-year-old nulligravid woman presenting to the gynecology clinic with one episode of intermenstrual bleeding, regular menstrual cycles with normal flow, and no history of dysmenorrhoea or dyspareunia. The genital local examination was normal, and speculum examination showed multiple vaginal lesions like polyps in the proximal posterior two-thirds and right lateral vaginal walls. Her transvaginal ultrasound read a normal uterus with a right ovarian simple cyst. The surgeon performed an outpatient operative vaginoscopy using a 5-mm continuous flow office hysteroscope with a 2.9-mm rod lens optical system and a 5F working channel. Distension of the vagina was achieved with a normal saline solution, and an intrauterine pressure of 50 to 60 mm Hg was maintained by an irrigation and aspiration electronic pump. An inspection of the vaginal walls, fornices, and the external cervical os (Fig. 1) revealed 10 vaginal lesions like polyps in the proximal two-thirds of the posterior and right lateral vaginal wall. The vaginal lesions (Fig. 2) varied in size from 0.5 cm to 4 cm. An excisional biopsy was performed and the sample sent for histopathologic evaluation. The vaginal lesions 2 cm were excised with the TruClear 5C Hysteroscopic Tissue Removal System (HTRS) with a zero-degree scope using the 2.9-mm incisor with a 5-mm cutting window at one end attached to a reusable handpiece with two connectors-one to the motor unit and second to the suction bottle with a collection bag. The overall diameter of TruClear 5C is 5.7 mm, and the optic size is 0.8 mm. The same irrigation pump is compatible with HTRS, and the pressure was increased to 150 mm Hg to maintain vaginal distension. Three factors influenced our decision to use the HTRS intraoperatively: the number and size of the vaginal lesions and the surgical time in the outpatient setting. A mechanical system that works on the principle of excising and aspirating tissue, the HTRS incisor has a rotatory action with the excising window placed against the most distal part of the vaginal lesions. The cutting action is controlled via a foot pedal attached to a motor control with 800 rotations per minute. The handpiece remains stationary while the polyp is excised and aspirated through the window into the collection bag. Minimal bleeding occurred and stopped spontaneously. The institutional ethics committee exempted this case report from review, and we obtained informed written consent from the patient. All vaginal lesions excised in an outpatient setting via vaginoscopy technique without anesthesia. The operative time with the Bettocchi hysteroscope was 14 minutes, and HTRS was 6 minutes. The patient did not complain of pain but did describe minimal discomfort, rated on the visual analog scale as 2 (where ≥5 is severe pain). She was discharged 1 hour later. The histopathology was reported as vaginal endometriosis (ectopic presentation of endometriosis is rare, accounting for 0.02% of cases). After surgery, she was started on cyclical oral contraceptive pills (OCP) in the combination of 30 mg of ethinyl estradiol + 2 mg of dienogest because she desired to delay pregnancy by 1 year. She remained asymptomatic for 6 months. These contraceptive hormones are available in the form of oral pills, vaginal rings, and transdermal patches, and a physician can provide OCP continuously or cyclically. Continuous OCP is more efficacious for control of dysmenorrhoea, but cyclical OCP is preferred because it is affordable, tolerable, effective, produces no unpredictable bleeding, and slows the progression of the disease. (A cohort study found the contraceptive vaginal ring to be more effective for symptom-control in rectovaginal endometriosis with higher patient satisfaction than the transdermal patch; vaginal rings or transdermal patches are not available in some countries.) CONCLUSION(S): Vaginoscopy allows a more in-depth visualization of the vagina with complete inspection and removal of all polyps. Vaginoscopy is feasible in the outpatient setting and allows a comfortable, ergonomic position for the surgeon. Vaginoscopy or no-touch technique avoids the use of a speculum or tenaculum and results in minimal pain during the outpatient procedure.

Reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer: a systematic review

This review sought to evaluate the current literature on reproductive and oncologic outcomes after fertility-sparing surgery for early stage cervical cancer (stage IA1-IB1) including cold-knife conization/simple trachelectomy, vaginal radical trachelectomy, abdominal radical trachelectomy, and laparoscopic radical trachelectomy with or without robotic assistance. A systematic review using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist to evaluate the current literature on fertility-sparing surgery for early stage cervical cancer and its subsequent clinical pregnancy rate, reproductive outcomes, and cancer recurrence was performed. Sixty-five studies were included encompassing 3,044 patients who underwent fertility-sparing surgery, including 1,047 pregnancies with reported reproductive outcomes. The mean clinical pregnancy rate of patients trying to conceive was 55.4%, with the highest clinical pregnancy rate after vaginal radical trachelectomy (67.5%). The mean live-birth rate was 67.9% in our study. Twenty percent of pregnancies after fertility-sparing surgery required assisted reproductive technology. The mean cancer recurrence rate was 3.2%, and the cancer death rate was 0.6% after a median follow-up period of 39.7 months with no statistically significant difference across surgical approaches. Fertility-sparing surgery is a reasonable alternative to traditional radical hysterectomy for early-stage cervical cancer in women desiring fertility preservation. Vaginal radical trachelectomy had the highest clinical pregnancy rate, and minimally invasive approaches to fertility-sparing surgery had equivalent oncologic outcomes compared with an abdominal approach. The results of our study allow for appropriate patient counseling preoperatively and highlight the importance of a multidisciplinary approach to achieve the best outcomes for each patient.

Infertility evaluation and treatment in cancer survivors

Necessity is the mother of ovarian tissue cryopreservation: Can we live up to the promise?

A misleading case of Müllerian anomaly: fibroid degeneration and growth involving nonfunctional, noncommunicating rudimentary horn

To report a rare, misleading fibroid degeneration involving a nonfunctional, noncommunicating horn in a woman with a unicornuate uterus. Although the presence of a functional rudimentary horn may lead to signs and symptoms that recommend its removal, nonfunctional cases are rarely reported, and because of their apparent functional inactivity, the need for their removal has not yet been reported. No previous report showed the possibility of a degenerative process in a nonfunctional rudimentary horn causing patient discomfort. This is a step-by-step narrated video showing a unique case of fibroid degeneration and growth of a nonfunctional, noncommunicating rudimentary horn in a unicornuate uterus (American Society for Reproductive Medicine classification 2021) and its surgical management. University academic hospital. A 48-year-old White nulliparous premenopausal woman was referred to our institution because of abdominal pain and an enlarging adnexal mass. Her personal history showed primary infertility with a previous diagnosis of unicornuate uterus. Given the possibility of ectopic ureters in these occurrences, complete computed tomography was performed, and no genitourinary alterations were found. Preoperative imaging (ultrasound evaluation, computed tomography, and magnetic resonance imaging) provided a provisional diagnosis of a suspicious ovarian fibroma. Considering the patient's age, lack of desire for pregnancy, and volumetric increase in the adnexal mass, a laparoscopic intervention to perform mass removal and prophylactic bilateral salpingectomy was planned. The patient was counseled about the low risk of an underlying malignant transformation. Therefore, the decision to remove the intact mass via a minilaparotomy at the end of the surgery was shared. Once the abdominal cavity was entered, the right unicornuate uterus was found in anatomical continuity with the ipsilateral broad ligament, fallopian tube, and ovary. These structures were wholly attached to the right pelvic wall. On the other side, cranially compared with the right hemiuterus, a roundish myoma-like mass was detected in direct connection with the left broad ligament, fallopian tube, and ovary. In light of a changed intraoperative finding, amputation of the left rudimentary horn and prophylactic bilateral salpingectomy were performed. Showing the fibroid degeneration and growth of a nonfunctional, noncommunicating rudimentary horn in a unicornuate uterus (American Society for Reproductive Medicine classification 2021) treated laparoscopically. Laparoscopic removal of the uterine horn was successful, and no intraoperative and postoperative complications occurred. The patient was in good health at the 6-month follow-up visit. The histopathological examination confirmed the fibroid degeneration and absence of the endometrium. The lack of symptomatic cases of rudimentary nonfunctional horns reported in the literature led gynecologists to consider them a silent Müllerian anomaly. This unique case demonstrates that even nonfunctional rudimentary horns can undergo symptomatic transformation processes requiring surgery. This information may be helpful for more comprehensive counseling of women and for considering the possibility of this occurrence in the diagnostic workup of misleading Müllerian anomalies. With this in mind, surgical treatment can also be better planned as the technical aspects change compared with what is expected for an adnexal pathology.

The role of minimal residual disease assessment in ovarian tissue cryopreservation among oncofertility cases

Fertility drugs and cancer: a guideline

Reply of the authors: Endometrial receptivity in adenomyosis and/or endometriosis

Step-by-step hysteroscopic treatment of International Federation of Gynaecology and Obstetrics type 3 myoma with the cold loop technique

To demonstrate the "cold loop technique" for the hysteroscopic treatment of International Federation of Gynaecology and Obstetrics (FIGO) type 3 myomas. Step-by-step demonstration of the technique using educative video. FIGO type 3 myomas exhibit complete myometrial development while encroaching on the endometrium. This hybrid nature, combining features of both submucous and intramural myomas, may have a detrimental "double hit" effect for patients seeking pregnancy. Currently, there is a dearth of robust evidence regarding the ideal surgical approach for FIGO type 3 myomas. Despite the preference for the hysteroscopic approach due to their closer proximity to the uterine cavity compared with the serosa, the primary limitations of the conventional hysteroscopic approach include the risks of damaging healthy myometrium and the significant risk of adhesions. We showcase the hysteroscopic treatment of a 29-mm FIGO type 3 myoma on the anterior uterine wall using the "cold loop technique." The video emphasizes key procedural phases: opening the "endometrial-myometrial window" with minimal sacrifice of myometrium; identifying the correct cleavage plane through blunt dissection of fibroconnective bridges anchoring the myoma to the pseudocapsule using cold loops; and slicing the detached intramural component of the fibroid, displaced into the uterine cavity, with an electrical loop. Integrity of the uterine cavity and the healthy myometrium surrounding the myoma and avoiding postsurgical intrauterine adhesions. The myoma was completely removed in a single surgical step, and at the end of the procedure, the myoma's "notch" and its intact pseudocapsule were clearly visible. The patient was discharged in good health the day after the surgery. At the 3-month follow-up, the diagnostic office hysteroscopy revealed a fully recovered uterine cavity. The "cold loop technique" holds the potential to facilitate the safe removal of FIGO type 3 myomas, minimizing the risk of damage to the adjacent healthy myometrium and resulting in a lower likelihood of postoperative adhesions. This is especially critical for women contemplating conception.

Targeted removal of a small gestational sac in early pregnancy loss via hysteroscopy: distinguishing the true gestational sac from two pseudogestational sacs and a submucosal fibroid

To demonstrate the techniques and advantages of targeted gestational sac removal via hysteroscopy in a case of early miscarriage. Video article. A 41-year-old woman with a missed miscarriage at 7 Non-contact hysteroscopy was conducted without uterine probing or cervical dilation using HEOS-mini hysteroscope (Delmont, France). The true gestational and pseudogestational sacs and submucosal fibroids were identified and removed using a grasper. Intraoperative intravenous oxytocin (10 IU in 500 mL normal saline) was administered to enhance the visualization of fibroids. Surgical skills were discussed in detail. This study was approved by the Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine (IIT2024-0505). Successful targeted removal of the gestational sac and intrauterine lesions. Cytogenetic analysis of the chorionic villi revealed a 45,XO karyotype. Histopathological findings confirmed the hysteroscopic diagnosis. The postoperative recovery was uneventful. Targeted removal of the gestational sac in early pregnancy loss via hysteroscopy is both feasible and effective. It offers valuable diagnostic and therapeutic benefits for patients with recurrent pregnancy loss who require precise sampling or those with concurrent intrauterine abnormalities.

Pregnancy and delivery outcomes after abdominal vs. laparoscopic myomectomy: an evaluation of an American population database

To evaluate population characteristics and obstetric complications after abdominal myomectomy vs. laparoscopic myomectomy. Retrospective cohort study. A total of 13,868 and 338 pregnancies after abdominal or laparoscopic myomectomy, respectively. Obstetrics outcomes following abdominal and laparoscopic myomectomy were collected. Obstetric outcomes after abdominal or laparoscopic myomectomies were collected using hospital discharges from 2004 to 2014 inclusively, and adjusted using multiple and binomial logistic regression in different models for age, obesity, chronic hypertension, and pregestational diabetes mellitus. Pregnancy, delivery, and neonatal outcomes were analyzed. Abdominal myomectomy were characterized by younger patients, lower rates of Caucasian, chronic hypertension, pregestational diabetes, active smoking, illicit drug use, and higher rates of previous cesarean delivery, and multiple gestations when compared with laparoscopic myomectomy. Pregnant women with laparoscopic myomectomy had decreased rates of pregnancy-induced hypertension (adjusted risk ratios [aRR], 0.12; 95% confidence intervals [CI], 0.006-0.24]), gestational hypertension (aRR, 0.24; 95% CI, 0.08-0.76), pre-eclampsia (aRR, 0.18; 95% CI, 0.07-0.48), and pre-eclampsia or eclampsia superimposed on chronic hypertension (aRR, 0.03; 95% CI, 0.005-0.3), gestational diabetes mellitus (aRR, 0.14; 95% CI, 0.06-0.34), preterm premature rupture of membranes (aRR, 0.14; 95% CI, 0.02-0.96), preterm delivery (aRR, 0.36; 95% CI, 0.23-0.55), and cesarean delivery (aRR, 0.01; 95% CI, 0.007-0.01) and small for gestational age (aRR, 0.15; 95% CI, 0.005-0.04), compared with abdominal myomectomy group. Laparoscopic myomectomy group had a higher rate of spontaneous (aRR, 35.57; 95% CI, 22.53-62.66), and operative vaginal delivery (aRR, 10.2; 95% CI, 8.3-12.56), uterine rupture (aRR, 6.1; 95% CI, 3.2-11.63), postpartum hemorrhage (aRR, 3.54; 95% CI, 2.62-4.8), hysterectomy (aRR, 7.74; 95% CI, 5.27-11.4), transfusion (aRR, 3.34; 95% CI, 2.54-4.4), pulmonary embolism (aRR, 7.44; 95% CI, 2.44-22.71), disseminated intravascular coagulation (aRR, 2.77; 95% CI, 1.47-5.21), maternal infection (aRR, 1.66; 95% CI, 1.1-2.5), death (aRR, 2.04; 95% CI, 1.31-3.2), and intrauterine fetal death (aRR, 2.99; 95% CI, 1.72-5.2) compared with the abdominal myomectomy group. Women who had a previous abdominal myomectomy have underlying risk factors for hypertension disorders of pregnancy and gestational diabetes. Women who underwent laparoscopic myomectomies have higher risks of bleeding, uterine rupture, resultant complications, and death, and should be monitored as high-risk patients, like abdominal myomectomies.

Advances in uterine fibroid research: linking progesterone and the transforming growth factor-β signaling pathway

Transvaginal radiofrequency ablation of a myoma in 10 key steps

To describe transvaginal radiofrequency ablation of myomas (TRAM) in 10 key steps. Video article. University hospital. A 38-year-old woman presented with menometrorrhagia and consequent chronic anemia (hemoglobin 8.5 g/dL) caused by a cervical myoma measuring 51 cm Not applicable. Volume of myoma and menometrorrhagia 6 months after treatment. Not applicable. Transvaginal radiofrequency ablation of myomas is a quick, simple, minimally invasive, and easily reproducible technique. It could be an interesting alternative to the conventional laparoscopic and open-surgical treatments of myomas. There is a lack of high-quality data establishing TRAM safety in infertility and pregnancy. The only available radiofrequency ablation device in the United States has specific language stating that this procedure is not recommended for women considering future pregnancy.

Uterine fibroid–related infertility: mechanisms and management

Fibroids are a common pathology and increasingly observed in women seeking medical treatment for infertility. The longer reproductive horizon because of improvements in medical care and current trend for women to postpone childbearing are making fibroid-related infertility increasingly common. This review aimed to critically analyze the association between uterine fibroids and infertility, mechanisms by which uterine fibroids may impair fertility, and management of myoma-related infertility. The association of fibroids with infertility is a source of controversy. As the focus of this review is infertility, it is crucial to analyze the mechanisms by which fertility may be impaired by the presence of fibroids. Current management strategies involve mainly surgical interventions, including myomectomy by hysteroscopy, laparotomy, or laparoscopy, and nonsurgical approaches, such as uterine artery embolization and focused ultrasound performed under radiologic or echographic guidance. The risks and benefits of each option should be discussed with patients, and several factors need to be considered, including the skills of surgeons and availability of different resources in various centers. Concerning the efficacy of oral gonadotropin-releasing hormone antagonists (i.e., elagolix, relugolix, and linzagolix), they were shown to have a rapid impact on heavy menstrual bleeding (HMB) in >70% of women. When used without add-back therapy, these drugs cause a significant reduction in fibroid volume, namely, approximately 50% from baseline to week 24. Further studies are required to determine the best protocol and optimal dosage if a reduction in myoma volume is the main goal, as in case of myoma-related infertility.

How and where to expect endosalpingiosis intraoperatively

To describe the anatomical distribution and intraoperative morphology of endosalpingiosis. Retrospective observational video study. Data and intraoperative videos were reviewed by two independent reviewers at one referral center. The study was approved by the local ethics committee. A total of 77 patients with histologically proven endosalpingiosis from 2007-2020. None. The primary endpoints were anatomical distribution and macroscopic phenotype. The secondary endpoints were demographic and clinical characteristics as well as associated diseases. Of the 77 patients with endosalpingiosis, the mean age was 40.2 years (standard deviation, 16.4 years), mean body mass index 24.1 kg/m In the majority of this population, endosalpingiosis was located in the pelvis. The higher prevalence of specific gynecologic tumors is consistent with previous results. In phenotype, most lesions appear to be less spectacular than prominent in the literature. For further studies on the relevance as a risk factor for malignancy and consequently clinical recommendations, sound knowledge about endosalpingiosis of laparoscopists as initial diagnosticians is crucial.

Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2

To assess the effects of relugolix combination therapy in women with uterine fibroids (UFs) and concomitant ultrasound-diagnosed adenomyosis. This post hoc analysis used pooled data from completers of the pivotal LIBERTY studies. The subgroup of women with adenomyosis and UFs was compared with the overall study population on selected efficacy and safety endpoints. Premenopausal women (aged 18-50 years) with diagnosed UFs (confirmed by ultrasonography) and heavy menstrual bleeding (assessed by the alkaline hematin method). Once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, and 0.5 mg of norethindrone acetate) or placebo for 24 weeks, or delayed relugolix combination therapy (40 mg of relugolix monotherapy for 12 weeks, followed by relugolix combination therapy for 12 weeks). Endpoints included the percentage of women with concomitant adenomyosis, the proportion of treatment responders (achieved or maintained a menstrual blood loss <80 mL and ≥50% reduction in menstrual blood loss volume from baseline over the last 35 days of treatment), the proportion of women achieving or maintaining amenorrhea over the last 35 days of treatment, and the change from baseline to week 24 in uterine volume and adverse events. A total of 111 women (18.2%) had a baseline diagnosis of concomitant adenomyosis (37 in the relugolix combination therapy group, 45 in the delayed relugolix combination therapy group, 29 in the placebo group) and were included in this analysis. Of women with adenomyosis, 83.8% in the relugolix combination therapy group were treatment responders compared with 27.6% in the placebo group. Amenorrhea was achieved in 64.9% of women with adenomyosis treated with relugolix combination therapy and in 6.9% of women treated with placebo. The least square mean uterine volume of women with adenomyosis decreased by 22.2% and 5.8% in the relugolix combination therapy and placebo groups, respectively. Results for the above outcomes in the relugolix combination therapy population were similar to the delayed relugolix combination therapy group. Efficacy outcomes in women with adenomyosis and UFs were comparable with those in women from the overall LIBERTY study population. LIBERTY 1, 2016-003727-27 (EudraCT) and NCT03049735; LIBERTY 2, 2016-005113-50 (EudraCT) and NCT03103087.

An umbrella review of meta-analyses regarding the incidence of female-specific malignancies after fertility treatment

Understanding the potential risks associated with fertility treatments (FTs) can guide clinical decision and patient counseling. To investigate the validity of the association between the development of female-specific malignancies including ovarian, endometrial, breast, and cervical cancer after FT. A search of systematic reviews and meta-analyses was performed from inception to April 2022 within several databases: Cochrane Database of Systematic Reviews, EMBASE, Google Scholar, and PubMed. The inclusion criteria required the incidence of each cancer subgroup to be stated in both the defined treatment group (controlled ovarian stimulation and/or in vitro fertilization [IVF] or intracytoplasmic sperm injection) and the control group (no-FT, general population). From 3,129 identified publications, 11 meta-analytical reviews consisting of 188 studies were selected for synthesis. The primary outcome of interest was incidence of each subgroup of cancer in the "FT" group compared with the "no-FT" group. A statistically significant increase in incidence of ovarian (1,229/430,611 in FT group vs. 27,358/4,263,300 in no-FT group) cancer (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.00-1.45) and borderline ovarian tumors (117/414,729 in FT group vs. 934/2,626,324 in no-FT group) (OR, 1.87; 95% CI, 1.18-2.97) was observed. The incidence of ovarian cancer was higher with FT and IVF specifically (OR, 1.65; 95% CI, 1.07-2.54). For borderline ovarian tumors, the incidence was higher, not only with FT overall and IVF, but also according to the fertility drug regimen applied: clomiphene citrate (CC) only (OR, 1.99; 95% CI, 1.02-3.87), human menopausal gonadotropin only (OR, 3.46; 95% CI, 1.39-8.59), and CC and human menopausal gonadotropin combined (OR, 3.79; 95% CI, 1.47-9.77). When using the threshold for statistical significance, the meta-analyses relevant to ovarian cancers remained statistically significant (random-effects method). However, none of the examined associations could claim either strong or highly suggestive evidence. An observed association between ovarian cancer (including borderline ovarian tumors) and FT has been demonstrated. The association between FT and female-specific malignancy remains a contentious topic because there have been contradictory outcomes among meta-analyses. This umbrella review interrogates existing systematic reviews and meta-analyses on this topic and concludes that a statistically significant increase in the incidence of ovarian cancer and borderline ovarian tumors is associated with FT. These findings have a significant clinical impact because it helps to inform and provide effective counseling for patients undergoing FT.

The impact of fibroid treatments on quality of life and mental health: a systematic review

Fibroids significantly impact the quality of life (QOL) and mental health of affected women. However, there are limited comparative data on QOL measures after medical, surgical, and radiologic interventions in women with fibroids. This study aimed to assess the current literature evaluating the impact of fibroids on QOL measures using several validated questionnaires for radiologic, medical, or surgical interventions or a combination of interventions before and after treatment. PubMed, PsycINFO, ClinicalTrials.gov, Embase, and Cochrane Library were searched from January 1990 to October 2023 to evaluate the available evidence, and the risk of bias was assessed using Cochrane RoB 2.0 or the Newcastle-Ottawa Scale. The review criteria included randomized controlled trials (RCTs) and observational cohort studies that included premenopausal women with symptomatic uterine fibroids, confirmed by imaging, who underwent an intervention to target fibroid disease. Only reports using validated questionnaires with a numerical baseline (pretreatment) and posttreatment scores were included. The exclusion criteria included perimenopausal or postmenopausal patients, conditions in addition to uterine fibroids that share similar symptoms, or studies that did not focus on QOL assessment. Abstracts were screened, and full texts were reviewed to determine whether studies met the inclusion criteria. A total of 67 studies were included after final review: 18 RCTs and 49 observational studies. All interventions were associated with a significant improvement in uterine fibroid-specific QOL measures, mental health metrics, and a reduction in symptom severity scores after treatment. These data reveal a substantial impact of uterine fibroids on the QOL and mental health of women with fibroids and indicate the metrics that can be used to compare the effectiveness of fibroid treatment options.

Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas

To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas. Laboratory study. Academic Research Institutions. This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland. Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments. Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed. The results indicated that progesterone activated the transforming growth factor-β and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-β (TGF-β) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology. We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-β and SMAD3 (SMAD3, TGF-β receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas.

Incidence of ovarian cancer after bilateral salpingo-oophorectomy in women with histologically proven endometriosis

To assess the incidence of ovarian cancer in women with histologically proven endometriosis after bilateral salpingo-oophorectomy (BSO). Retrospective nationwide cohort study. Dutch pathology database. Women with histologically proven endometriosis who had undergone BSO between 1990 and 2015 (n = 7,984). This study consists of 2 control cohorts: women with histologically proven endometriosis without BSO (n = 42,633) and women with a benign dermal nevus (n = 132,535). Observational study. Number of histologic diagnoses of (extra-)ovarian cancers. Incidence rate ratios (IRR) were estimated for (extra-)ovarian cancer. The number needed to treat was calculated. We identified 9 (0.1%) (extra-)ovarian cancers in the BSO cohort and 170 (0.4%) and 444 (0.3%) ovarian cancers in the endometriosis and nevus control cohorts, respectively. We found an age-adjusted IRR of 0.34 (95% confidence interval [CI], 0.15-0.76) when the BSO cohort was compared with the endometriosis cohort. Comparing the BSO cohort with the nevus control cohort resulted in an age-adjusted IRR of 0.38 (95% CI, 0.17-0.85). The number needed to treat when the BSO cohort was compared with the endometriosis control cohort was 351 (95% CI, 272-591). In this nationwide study, we found that the (extra-)ovarian cancer incidence in women with histologically proven endometriosis decreased to less than the background population risk after BSO. Additionally, we found a significant reduction of the incidence of ovarian cancer when compared with women with histologically proven endometriosis without BSO. Endometriosis surgery could in the future be a preventive strategy in women with endometriosis and a high-risk profile for ovarian cancer.

Effects of risk factors for ovarian cancer in women with and without endometriosis

To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis. Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium. Population-based. We included 8,500 women with ovarian cancer, 13,592 control women. Ten well-established ovarian cancer risk factors. Risk of ovarian cancer for women with and without endometriosis. Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-<30 kg/m The associations between ovarian cancer and most risk factors were similar among women with and without endometriosis. However, there was some suggestion of differences by endometriosis status for BMI, menopausal hormone therapy use, and genital talcum powder use, highlighting the complexity of ovarian cancer etiology.

Is it time to broaden the scope of fertility-sparing treatments for early-stage cervical cancer?

An effective method using laparoscopy in treatment of upper vaginal leiomyoma

To introduce an effective approach using laparoscopy in the treatment of upper vaginal leiomyoma. Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique, approved by the Shengjing Hospital of China Medical University. Hospital. A 34-year-old woman diagnosed with 5-cm upper vaginal leiomyoma, who had sexual discomfort for 5 years. Using laparoscopy in the treatment of upper vaginal leiomyoma consists of five steps: first lysing the pelvic adhesion; exploring the pelvic cavity and locating the vaginal leiomyoma through gynecologic examination by the assistant; recognizing the position between leiomyoma and ureter and carefully dissociating ureter while avoiding injury; completely enucleating and resecting the vaginal leiomyoma using laparoscopy; and exploring the ureter, rectum, and uterine artery to make sure there was no injury. Value and feasibility of using laparoscopy in treatment of upper vaginal leiomyoma. The vaginal leiomyoma was removed successfully using laparoscopic operation and the operative time was 95 minutes. In the follow-up period, the patient did not report any symptoms, and she became pregnant at the time of the 20th month after operation and underwent a vaginal delivery at full-term. For upper vaginal leiomyoma treatment, laparoscopic operation could present a clear visual field to avoid injury of bladder, ureter, rectum, and uterine artery. Laparoscopic operation is safe and feasible in treatment of upper vaginal leiomyoma.

Neoadjuvant chemotherapy followed by conization in stage IB2–IIA1 cervical cancer larger than 2 cm: a pilot study

To evaluate feasibility of neoadjuvant chemotherapy (NACT) followed by cold-knife conization (CKC) in patients with 2018 FIGO stage IB2-IIA1 cervical cancer who desired to maintain fertility. Pilot study of conization after chemotherapy in stage IB2-IIA1 >2 cm cervical cancer. University hospital. From 2014 to 2018, 25 patients, <40 years of age, were enrolled. After laparoscopic pelvic lymph-node assessment, NACT with cisplatin/paclitaxel q21 was administered to eligible patients. Responsive patients were treated with CKC. Obstetrical outcome: pregnancy rate. Oncologic outcome. Thirteen out of 25 patients were eligible for fertility-sparing treatment. Oncologic outcome: The clinical overall response rate was 84.5% (11 out of 13 patients). One patient achieved stable disease, was managed by radical surgery, and is still alive; another one experienced progression of disease and died after 15 months. The optimal pathologic response was 69.1%. In the setting of fertility preservation patients, the median follow-up was 37 months (range 18-76). In this group we registered one distant recurrence, 12 months after CKC, in the liver; the patient is still alive and without evidence of disease. Obstetrical outcome: Among the nine patients amenable, three tried to conceive, and two spontaneous pregnancy occurred a few months after the end of treatment, for a pregnancy rate of 66.7%. This pilot study supports the feasibility of CKC after NACT as conservative treatment in stage IB2-IIA1 cervical cancer, with oncologic outcomes similar to those reported for trachelectomy in the same stage and with potential benefits in terms of obstetrical outcomes. NCT02323841.

An update on uterine cervix pathologies related to infertility

Many papers and reviews have described the changes of the cervix during pregnancy, cervical cancer, sexually transmitted infections, and cervicovaginal microbiota. In this Views and Reviews, we focus on some specific topics in relation to the uterine cervix and infertility: early cervical cancer and fertility sparing surgery, cesarean scar defect, cervical incompetence, and cervical müllerian anomalies.