Paula C. Brady

Uterine fibroids and subfertility: an update on the role of myomectomy.

Purpose of review Uterine fibroids, the most common neoplasm of reproductive-aged women, can have a significant impact on quality of life, and may affect fertility and pregnancy outcomes. Although it is generally accepted that submucosal fibroids are of clinical significance, the effect of intramural and subserosal fibroids, and the benefit of surgical removal remains an area of active debate. Because of this controversy, this article will review current evidence for an association of fibroids and subfertility, and assess the impact of surgical management on fertility outcomes. Recent findings Recent analyses of patients with intramural fibroids have reported an increase in pregnancy loss and reduction in pregnancy and live birth rates. However, when analyzing studies with high quality diagnostic methods for assessing the endometrial cavity, no significant impact on reproductive outcomes was observed, and no benefit of myomectomy was consistently demonstrated. Myomectomy for submucosal fibroids greater than 2 cm and for intramural fibroids distorting the endometrial contour likely confers improvement of fertility outcome. Summary Submucosal fibroid location and distortion of the endometrial cavity (either submucosal or deeply infiltrating intramural fibroids) are most predictive of impaired fertility and probable benefit of surgical removal, and warrant consideration of myomectomy in the subfertile patient.

Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review

BackgroundEctopic pregnancy is a potentially life-threatening condition occurring in 1-2 % of all pregnancies. The most common ectopic implantation site is the fallopian tube, though 10 % of ectopic pregnancies implant in the cervix, ovary, myometrium, interstitial portion of the fallopian tube, abdominal cavity or within a cesarean section scar.FindingsDiagnosis involves a combination of clinical symptoms, serology, and ultrasound. Medical management is a safe and effective option in most clinically stable patients. Patients who have failed medical management, are ineligible, or present with ruptured ectopic pregnancy or heterotopic pregnancy are most often managed with excision by laparoscopy or, less commonly, laparotomy. Management of nontubal ectopic pregnancies may involve medical or surgical treatment, or a combination, as dictated by ectopic pregnancy location and the patients clinical stability. Following tubal ectopic pregnancy, the rate of subsequent intrauterine pregnancy is high and independent of treatment modality.ConclusionThis review describes the incidence, risk factors, diagnosis, and management of tubal and non-tubal ectopic and heterotopic pregnancies, and reviews the existing data regarding recurrence and future fertility.

Early beta-human chorionic gonadotropin trends in vanishing twin pregnancies

OBJECTIVE To describe the early β-hCG trends in vanishing twins compared with normally progressing singleton and twin pregnancies. DESIGN Retrospective cohort study. SETTING University-based infertility clinic. PATIENT(S) Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 1998 and 2010. INTERVENTION(S) Early β-hCG level increase in vanished twin pregnancies was compared with the level increase in normally progressing singleton and twin pregnancies. MAIN OUTCOME MEASURE(S) Two-day percent increase in β-hCG level. RESULT(S) Pregnancies with vanishing twins demonstrated a significantly lower mean 2-day percent increase in β-hCG level than singletons and twins (114.3% vs. 128.8% and 125.4%, respectively). Vanishing twins arresting at earlier developmental stages demonstrated significantly further reduced β-hCG level increases. Infrequently, all groups had β-hCG level increases less than previously established clinical thresholds that led to a live birth. CONCLUSION(S) Early β-hCG level increases are slower in vanishing twins than in singleton and twin pregnancies, with the slowest increases seen when the spontaneous fetal losses occur at earlier developmental stages. All increases, however, are within clinically accepted normal limits. Therefore, abnormal β-hCG level increases should not be attributed to a vanishing twin. Of note, an abnormal β-hCG level trend--even an initial decrease--does not preclude live birth, even in a singleton pregnancy.

Pregnancies of unknown location after in vitro fertilization: minimally invasive management with Karman cannula aspiration

OBJECTIVE To describe a standardized protocol for the assessment of asymptomatic patients with pregnancies of unknown location (PUL) after IVF. DESIGN Retrospective cohort study. SETTING University-based infertility clinic. PATIENT(S) Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 2005 and 2011. INTERVENTION(S) Endometrial sampling using Karman suction cannula in patients with PUL and abnormal β-hCG trend (increase <53% or decrease <15% in 2 days) and a pelvic ultrasound unremarkable for an intrauterine pregnancy (IUP) or an ectopic pregnancy (EP). MAIN OUTCOME MEASURE(S) Proportion of patients spared methotrexate (MTX) administration. RESULT(S) Endometrial sampling was performed in 45 patients. Of these, 31 (68.9%) were diagnosed with failed IUP by either a sampling after the β-hCG decline (≥15%) and/or the presence of villi on final pathology. No further intervention was required. Fourteen patients (31.1%) were diagnosed with presumed EP by persistent β-hCG level after negative pathology. Ten of these patients (71%) were successfully treated with a single dose of MTX; three required an additional dose, and one required laparoscopy for a ruptured EP. CONCLUSION(S) In asymptomatic patients with PUL and abnormal β-hCG trends after IVF, the utility of Karman aspiration to confirm an IUP may obviate treatment with MTX in more than two-thirds of patients.

Dynamic antimüllerian hormone levels during controlled ovarian hyperstimulation predict in vitro fertilization response and pregnancy outcomes

OBJECTIVE To evaluate the patterns of change in serum antimüllerian hormone (AMH) during controlled ovarian hyperstimulation (COH) and their relation to concurrent response and in vitro fertilization (IVF) pregnancy outcomes. DESIGN Prospective cohort study. SETTING Academic medical center. PATIENT(S) A total of 113 consecutive fresh IVF embryo transfer cycles from September 1, 2012 through January 1, 2013. INTERVENTION(S) Serial serum AMH measurements were analyzed on each day that serum estradiol (E2) was drawn during COH. MAIN OUTCOME MEASURE(S) Relationship between the rate of COH AMH change [Δ ng/mL per day] (stratified into tertiles), and ovarian response, and pregnancy outcomes. RESULT(S) During COH, AMH declined. Age and ovarian reserve testing were associated with the rate of AMH decline (RAD). Women with intermediate and minimal RAD had statistically significantly fewer follicles ≥ 12 mm, lower peak serum E2, fewer oocytes, and inferior early embryo development compared with women with the greatest RAD. Compared with patients with the lowest RAD, clinical pregnancy was more likely in patients with the greatest RAD in the total population (adjusted odds ratio 3.51; 95% confidence interval, 1.03, 11.94) and among patients older than 35 years (adjusted odds ratio 6.95; 95% confidence interval, 1.09, 44.1). CONCLUSION(S) The rate of COH AMH decline was associated with ovarian reserve testing, oocyte yield, embryo progression, and clinical pregnancy rates, particularly in women older than 35 years. These results suggest that dynamic AMH levels may provide a novel intracycle approach to predict response and treatment outcomes after IVF.

Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location

BACKGROUND: Pregnancies of unknown location with abnormal beta‐human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. OBJECTIVE: The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. STUDY DESIGN: A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta‐human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta‐human chorionic gonadotropin trend (<53% rise or <15% fall in 2 days). These patients underwent outpatient endometrial sampling with Karman cannula aspiration. Patients with a beta‐human chorionic gonadotropin decline ≥15% within 24 hours of sampling and/or villi detected on pathologic analysis were diagnosed with failing intrauterine pregnancy and had weekly beta‐human chorionic gonadotropin measurements thereafter. Those patients with beta‐human chorionic gonadotropin declines <15% and no villi identified were diagnosed with ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m2) or laparoscopy. RESULTS: Across 8 years of follow up, among women with pregnancy of unknown location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta‐human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta‐human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta‐human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; P<.001). CONCLUSION: With the use of this safe and effective protocol of endometrial aspiration with Karman cannula, a large proportion of women with pregnancy of unknown location are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate.

Large Asymptomatic FIGO Type 3–5 Fibroid and Primary Infertility

The patient is a 30-year-old healthy nulligravid patient diagnosed with an 8 centimeter (cm) intramural fibroid (FIGO type 3–5) [1].

Fertility preservation in women with marrow failure syndromes prior to allogeneic stem cell transplantation

Except Patient A, who was alloimmunized to RBCs, six patients received transfusions before receiving voxelotor, whereas 2 of 6 patients received no transfusions afterward. Baseline oxygen saturation for patients A, C, D, and E was <95%, which improved to 98%-99% with voxelotor treatment, allowing Patients A and E to discontinue long-term supplemental oxygen. Patient A, who had a 6MWT at baseline and after 14 and 24 weeks of voxelotor treatment, experienced steady improvements in distance walked (330 m, 375 m, and 387 m, respectively), post-walk pulse rate (102 beats per minute [bpm], 96 bpm, and 93 bpm, respectively), and post-walk room air oxygen partial pressure (86%, 93%, and 96%, respectively) over the course of treatment. Most patients experienced improved well-being typically 2–3 weeks after starting voxelotor treatment. Although this is partially reflected in pain assessments at clinic visits, a more informative measure involved hospitalizations for vaso-occlusive crisis (VOC) pain. The number of hospitalizations for VOC pain decreased by 67% in the 24 weeks after voxelotor initiation compared with the 24 weeks before treatment initiation (9 vs. 28; Supporting Information Figure 2). The number of hospitalizations per patient ranged from 2 to 5 during the 24 weeks before voxelotor, and that number decreased in all patients during the 24 weeks of treatment. Two patients had no hospitalizations after treatment initiation, and the number of hospitalizations decreased by half for four other patients. At baseline, Patient D had moderate depression and Patient A had moderately severe depression, whereas five patients had no/minimal depression, as assessed by the PHQ-9 (Table 1). After 24 weeks of treatment with voxelotor, affect improved in Patients A and D, with Patient A showing no/minimal depression and Patient D showing mild depression. Through this compassionate use activity, the seven patients described here, who had exhausted all treatment options, demonstrated several meaningful improvements, including increased Hb levels, improved oxygen saturation, and fewer transfusions and hospitalizations for VOC. Although the patients were followed closely with structured data collection, this is an uncontrolled case series and cannot be equated with data from a controlled clinical trial. Nonetheless, the consistency, robustness, and durability of response to voxelotor in these patients with severe SCD is encouraging and support the ongoing clinical trials to assess the safety and efficacy of voxelotor in patients with SCD, including the phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) study for patients with SCD aged 12 years and older (clinicaltrials.gov identifier, NCT03036813).

An Updated Review of Ectopic Pregnancies Resulting from Assisted Reproduction

Purpose of ReviewThe purpose of this study was to review the most recent data regarding clinical risk factors for ectopic pregnancy (EP) among patients pursuing assisted reproduction, and the diagnosis and management of EP in this specific population.Recent FindingsEP rates following assisted reproduction have fallen over time to 1–2%, identical to the general population. Clinical risk factors for EP following assisted reproduction include the transfer of autologous, fresh and cleavage-stage embryos. Use of a GnRH agonist trigger alone for fresh cycles is associated with a greater risk of EP than hCG trigger. Serial hCG measurements and transvaginal ultrasound remain the mainstay of EP diagnosis. The addition of endometrial sampling to exclude failing intrauterine pregnancy spares a majority of patients unnecessary methotrexate. Two recent meta-analyses confirm that methotrexate for EP does not diminish subsequent response to controlled ovarian hyperstimulation (COH), while data conflict regarding the effects of salpingectomy on subsequent ovarian response. A recent randomized controlled trial, primarily in a non-infertility population, showed similar rates of subsequent intrauterine pregnancy following salpingectomy or salpingostomy in the presence of normal contralateral fallopian tubes. A large population-based study confirmed this finding, but reported higher ongoing pregnancy rates following tubal preservation in patients with infertility or tubal disease attempting natural conception.SummaryThe risk of EP following IVF appears largely mediated by altered endometrial receptivity, shown to result from COH and GnRH agonist-only triggers. Transfer of frozen-thawed blastocysts confers the lowest rate of EP following IVF. Methotrexate does not impact subsequent ovarian response to stimulation, though the effects of salpingectomy remain to be determined. Salpingectomy and salpingostomy confer equitable subsequent ongoing pregnancy rates, though tubal preservation may confer an advantage in women with tubal disease or infertility planning natural conception.

Vulvovaginal Dermatoses, Lesions, and Masses

Vulvar lesions, rashes, and pruritis are common complaints. This chapter includes the differential diagnosis of vulvar symptoms divided among infectious and noninfectious causes and by lesion characteristic (abscesses, blisters or desquamation, ulcers, fissures, and masses). Diagnosis (by history, physical exam, serology, cultures, or biopsy) and management of specific etiologies are discussed.