Three-dimensional ultrasound diagnosis of T-shaped uterus is associated with adverse pregnancy outcomes after embryo transfer.

RESEARCH QUESTION: Is T-shaped uterine cavity morphology associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst? DESIGN: In this secondary analysis of a prospective cohort study, 648 patients with three-dimensional ultrasound (3D-US) data obtained on the day before embryo transfer were categorized into three groups according to uterine cavity morphology: normal (n = 472), intermediate (n = 166) and T-shaped (n = 10). Quantitative uterine cavity dimensions were used to evaluate uterine cavity morphology. Pregnancy outcomes, including live birth, clinical miscarriage and ectopic pregnancy, were compared among the groups. RESULTS: The prevalence of a T-shaped uterus in this cohort was 1.5%. Uterine cavity morphology was strongly associated with the ratio of interostial distance and isthmic diameter (P < 0.01). Live birth rates were 66.5% for normal, 65.7% for intermediate and 40.0% for T-shaped cavity morphology. Women with a T-shaped uterus had an increased risk of clinical miscarriage (40.0% versus 7.0% for normal and 9.0% for intermediate cavity morphology, P < 0.01) and ectopic pregnancy (10.0% versus 1.1% for normal and 1.9% for intermediate cavity morphology, P = 0.05). When evaluating interostial distance and isthmic diameter ratio to determine pregnancy outcomes, a cut-off value of 2 was noted to have weak predictive value for live birth, but not clinical miscarriage or ectopic pregnancy. CONCLUSIONS: T-shaped uterine cavity morphology is associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst. Given the low prevalence of this condition, quantifying the magnitude of risk will require a larger cohort of patients.

ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation.

Focal adhesions anchor cells to extracellular matrix (ECM) and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC) focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM.

Minimally Invasive Approaches to Myoma Management.

Patients affected by the presence of leiomyomas may incur a substantial physical, emotional, social, and financial toll as well as losses in their quality of life. Although many myomas are not amenable to medical therapy or hysteroscopic resection, many others are amenable to minimally invasive surgical approaches. In patients who prefer to retain their fertility, laparoscopic myomectomy should be considered the intervention of choice. In this review, we expand on the surgical techniques of both conventional laparoscopic and robotic-assisted myomectomies. We discuss port placement, enucleation of myomas, tissue extraction, minimization of blood loss, adhesion prevention, and the technique for closure of uterine incisions. Finally, we discuss the available data supporting the use of these 2 approaches as the preferred, safe, and effective fertility-sparing surgical option. We also briefly discuss the emerging technologies of uterine artery embolization, ultrasound surgery, and radiofrequency ablation.

Versatility of the suprapubic port in robotic assisted laparoscopic myomectomy.

OBJECTIVE: To demonstrate the multiple advantages of the suprapubic port in robotic assisted laparoscopic myomectomy. DESIGN: Video demonstration of a robotic assisted laparoscopic myomectomy technique using a suprapubic incisional retractor (GelPOINT). SETTING: Hospital. PATIENT(S): A 32-year-old primigravid women with heavy menstrual bleeding and pelvic pain with a 12-cm leiomyoma (International Federation of Gynecology and Obstetrics type 5). INTERVENTION(S): Illustrate a surgical approach during robotic assisted laparoscopic myomectomy with the use of a 5-cm suprapubic incision, an incisional retractor (GelPOINT) for the enucleation, and extraction of a large leiomyoma. MAIN OUTCOME MEASURE(S): The effective enucleation and extraction of a leiomyoma specimen using an incisional retractor and GelPOINT. The steps of the technique and the role of GelPOINT are demonstrated. RESULT(S): The procedure was performed without incident, and the patient experienced pain relief and lighter menses postoperatively. This technique has been performed successfully since June 2014 on 22 women. CONCLUSION(S): During a robotic assisted laparoscopic myomectomy the suprapubic incision is both advantageous and practical. The small incision allows the surgery to remain minimally invasive; the primary umbilical trocar is inserted under direct visualization in an already insufflated abdomen; the location of the incision allows the surgical assistant easy access to the port; the passing of the needles occurs under direct visualization with minimal camera manipulation; and last, the extraction of large tissue can be performed within a specimen pouch through this same suprapubic incision in a short period.

Versican Proteolysis by ADAMTS Proteases and Its Influence on Sex Steroid Receptor Expression in Uterine Leiomyoma.

Context: Leiomyomas have abundant extracellular matrix (ECM), with upregulation of versican, a large proteoglycan. Objective: We investigated ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs) protease-mediated versican cleavage in myometrium and leiomyoma and the effect of versican knockdown in leiomyoma cells. Design: We used quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and RNA in situ hybridization for analysis of myometrium, leiomyoma and immortalized myometrium and leiomyoma cells. Short interfering RNA (siRNA) was used to knockdown versican in leiomyoma cells. Setting: This study was performed in an academic laboratory. Patients: Study subjects were women with symptomatic or asymptomatic leiomyoma. Main Outcome Measures: We quantified messenger RNAs (mRNAs) for versican splice variants. We identified ADAMTS-cleaved versican in myometrium and leiomyoma and ADAMTS messenger RNAs and examined the effect of VCAN siRNA on smooth muscle differentiation and expression of estrogen and progesterone receptors. Results: The women in the symptomatic group (n = 7) had larger leiomyoma (P = 0.01), heavy menstrual bleeding (P < 0.01), and lower hemoglobin levels (P = 0.02) compared with the asymptomatic group (n = 7), but were similar in age and menopausal status. Versican V0 and V1 isoforms were upregulated in the leiomyomas of symptomatic versus asymptomatic women (P = 0.03 and P = 0.04, respectively). Abundant cleaved versican was detected in leiomyoma and myometrium, as well as in myometrial and leiomyoma cell lines. ADAMTS4 (P = 0.03) and ADAMTS15 (P = 0.04) were upregulated in symptomatic leiomyomas. VCAN siRNA did not effect cell proliferation, apoptosis, or smooth muscle markers, but reduced ESR1 and PR-A expression (P = 0.001 and P = 0.002, respectively). Conclusions: Versican in myometrium, leiomyomas and in the corresponding immortalized cells is cleaved by ADAMTS proteases. VCAN siRNA suppresses production of estrogen receptor 1 and progesterone receptor-A. These findings have implications for leiomyoma growth.

The medical management of abnormal uterine bleeding in reproductive-aged women.

In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention.

Uniparental disomy in the human blastocyst is exceedingly rare.

OBJECTIVE: To establish whether uniparental disomy (UPD) could represent an outcome of embryonic aneuploidy self-correction and its relevance to preimplantation genetic diagnosis, and to validate a method of UPD detection in limited quantities of cells and determine the frequency of UPD in a large sample size of human blastocysts. DESIGN: Retrospective observational. SETTING: Academic center for reproductive medicine. PATIENT(S): Couples undergoing in vitro fertilization (IVF) treatment whose embryos underwent trophectoderm biopsy single-nucleotide polymorphism (SNP) array-based 24-chromosome aneuploidy screening. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rate of UPD observed in the human blastocyst. RESULT(S): After application of defined thresholds, 2 of 3,401 blastocysts were found to possess isodisomy, and 0 were found to possess heterodisomy. The overall frequency of UPD in the human blastocyst was therefore 0.06%. CONCLUSION(S): This validated method of detection indicates that UPD is extremely rare and suggests that routine screening during preimplantation genetic diagnosis (PGD) may not be necessary. Furthermore, chromosomal UPD is unlikely to explain or support the existence of embryonic self-correction.

Vulvar endometriosis presenting with dyspareunia: a case report.

BACKGROUND: Superficial dyspareunia can be caused by a multitude of medical and psychological conditions, including pathologic conditions of the vulva. Although infectious and inflammatory causes are more common, vulvar endometriosis is a rare and often overlooked etiology of dyspareunia. CASE: A 33-year-old woman, gravida 1, para 1, presented for a gynecologic consultation with a 2-year history of increasing dyspareunia and cyclical vulvar pain associated with a vulvar mass. Previous treatment with analgesics and sitz baths did not alleviate the symptoms. Pelvic examination revealed a right Bartholin's gland mass that was tender to palpation. The working diagnosis was a Bartholin's cyst as the cause of the dyspareunia, and the patient was scheduled for marsupialization and/or resection. Examination under anesthesia revealed an irregular, 5 cm, solid mass that extended into the labia majora, which was excised. Pathologic examination of the mass revealed endometriosis. The postoperative course was unremarkable and the patient reported complete resolution of symptoms. CONCLUSION: This case illustrates that superficial dyspareunia associated with cyclical vulvar pain can be caused by endometriosis involving the labia majora.

Family planning attitudes of medically underserved Latinas.

OBJECTIVE: To evaluate the cultural and socioeconomic factors that may influence family planning decisions in Latinas attending a community health center. METHODS: Contraceptive choices made by medically underserved Latinas attending a federally funded community health clinic were surveyed, and the societal, religious, economic, and community factors that affect their use were evaluated. RESULTS: In a cohort of 97 Latinas, almost one third were not using birth control, and those using birth control often chose nonhormonal methods. Early pregnancy was desired by this cohort, with 72 women (84%) reporting that 25 years or younger was an ideal age for a first pregnancy; 81 women (89 %) indicated having children was an extremely important goal for them. CONCLUSIONS: Contraceptive use was lower than the national average in this cohort of mainly Spanish-speaking Latinas, with most of the women using methods considered not as efficacious as hormonal ones. These data suggest that initial counseling for young Latinas, especially for those who may not be acclimated to U.S. culture as evidenced by their preference for counseling in Spanish, should focus on how to optimally prepare for planning and spacing of pregnancies rather than on how to prevent pregnancy. Counseling that emphasizes only birth control options and not pregnancy concerns should be employed after desired family size is reached.