Association between arthritis treatments and ovarian reserve: a prospective study.

RESEARCH QUESTION: How do anti-Müllerian hormone (AMH) concentrations in women with and without arthritis compare? Is there an association between AMH and arthritis drug regimen? DESIGN: In this prospective cohort study, AMH was measured at two time points (T0 and T1) in 129 premenopausal women with arthritis. AMH at T0 was compared with that from a bank of serum samples from 198 premenopausal women without arthritis. Primary outcomes were: (i) diminished ovarian reserve (DOR) (AMH <1.1 ng/ml) and (ii) annual rate of AMH decrease. Univariate, multivariable and Firth logistic regression identified variables associated with annual AMH decrease in excess of the 75th percentile. RESULTS: Median time between T0 and T1 was 1.72 years. At time T0, median age-adjusted AMH in women with arthritis was significantly lower than that of women without arthritis (median 2.21 ng/ml versus 2.78 ng/ml; P = 0.009). Women with arthritis at highest risk for DOR had a history of tubal sterilization or were over the age of 35. Those with highest odds of having an annual AMH decrease in excess of the 75th percentile (over 28% decrease per year) were those: over the age of 35 or who sought care for infertility. Women with arthritis taking methotrexate alone (OR 0.08, 95% CI 0.01-0.67) or methotrexate plus tumour necrosis factor-alpha antagonists (OR 0.13, 95% CI 0.02-0.89) were less likely to be in the highest quartile of annual AMH decrease than women with arthritis not taking medication. CONCLUSIONS: Women with arthritis had lower AMH than healthy controls. Long-term methotrexate use was not associated with an annual AMH decrease.

Imaging of the Vagina: Spectrum of Disease with Emphasis on MRI Appearance.

The vagina is a median fibromuscular structure of the female reproductive system that extends from the vulva inferiorly to the uterine cervix superiorly. As most vaginal lesions are detected at gynecologic examination, imaging performed for nongynecologic indications can frequently cause concomitant vaginal pathologic conditions to be overlooked. The vagina is often underevaluated at routinely performed pelvic transvaginal US because of a narrow scan area and probe positioning. MRI has progressively become the imaging method of choice for vaginal pathologic conditions, as it provides excellent soft-tissue detail with unparalleled delineation of the complex pelvic floor anatomy and helps establish a diagnosis for most vaginal diseases. It is important that radiologists use a focused approach toward understanding and correctly recognizing different vaginal entities that may otherwise go unnoticed. In this case-based review, the authors discuss the key imaging features of wide-ranging vaginal pathologic conditions, with emphasis on appearance at MRI. Knowledge of vaginal anatomy and embryology is helpful in evaluating congenital anomalies at imaging. Often seen incidentally, vaginal inflammation can cause diagnostic confusion. Because of its central location in the pelvis, the vagina can form fistulas to the urinary bladder, colon, rectum, or anus. Vaginal masses can be neoplastic and nonneoplastic and include a myriad of benign and malignant conditions, some of which have characteristic imaging features. Therapeutic and nontherapeutic vaginal foreign bodies include pessaries, vaginal mesh, and packing that can be seen with or without associated complications. Online supplemental material is available for this article. ©RSNA, 2021.

Correction to: Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial.

The original version of this article unfortunately contained mistakes. The complete list of corrections is given below.

Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial.

PURPOSE: Implantation failure is a major limiting factor of successful in vitro fertilization (IVF). The objective of this study was to determine if endometrial mechanical stimulation (EMS) by endometrial biopsy in the luteal phase of the cycle prior to embryo transfer (ET) improves clinical outcomes in an unselected subfertile population. METHODS: Double-blind, randomized controlled trial of EMS versus sham biopsy and odds of clinical pregnancy after IVF and embryo transfer. Secondary outcomes included spontaneous miscarriage and live birth. RESULTS: One hundred women enrolled and were randomized from 2013 to 2017. Enrollment was terminated after futility analysis showed no difference in clinical pregnancy between EMS versus control, 47.2% vs 61.7% (OR 0.55, 95% CI 0.25-1.23, p = 0.15). There were no significant differences between women who underwent EMS and those who did not in terms of positive pregnancy test 54.7% vs 63.8% (OR 0.69, 95% CI 0.31-1.53, p = 0.36), miscarriage 7.5% vs 2.1% (OR 3.76 95% CI 0.41-34.85, p = 0.22), or live birth 43.4% vs 61.7% (OR 0.48 95% CI 0.21-1.06, p = 0.07). CONCLUSIONS: EMS in the luteal phase of the cycle preceding embryo transfer does not improve clinical outcomes in an unselected subfertile population and may result in a lower live birth rate. We caution the routine use of EMS in an unselected population.

Antral follicle count is increased in obese women placed on oral contraceptive pills.

OBJECTIVE: To determine the effect of short-term combined oral contraceptive (OCP) use on antral follicle count (AFC) in obese and nonobese women with infertility. STUDY DESIGN: A retrospective review of women who had an AFC (sum of 2-10 mm bilateral ovarian follicles on basal follicular phase ultrasound) measured before and after short-term OCP use between the years 2005 and 2010. These were women who had a baseline AFC measurement during an unsuccessful controlled ovarian hyperstimulation/intrauterine insemination who were then placed on OCPs prior to an in vitro fertilization (IVF) cycle that included a subsequent AFC measurement at baseline. RESULTS: A total of 57 IVF cycles met criteria for inclusion in the study. AFC was not impacted by OCP use in the nonobese cohort (BMI < 30). Baseline AFC in obese women (BMI ≥ 30), however, increased after OCP use (18 ± 6 vs. 28 ± 9, p = 0.002). CONCLUSION: Use of suppressive medications like OCPs in obese women increases AFC during IVF, potentially by AFC cohort synchrony. This observation warrants consideration when using AFC to predict gonadotropin/ART response as well as future prospective research to further elucidate potential etiologies.

Severe ovarian hyperstimulation syndrome in patients with autoimmune disorders: a report of two cases.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) following ovulation induction is common and varies in severity from mild to severe. Severe OHSS can be life threatening and requires hospitalization and procedures to reduce the extracellular fluid accumulation. Ovulation induction regimen and patient characteristics such as young age and low body weight have been identified as risk factors for OHSS, and follicle count >20 may be predictive of increased risk for moderate to severe OHSS. Whether any other patient factors are important in this risk equation is unknown. CASES: We report on 2 patients with type 1 diabetes mellitus (T1DM) and other autoimmune diseases who experienced a total of 4 episodes of OHSS, 2 of which were severe. CONCLUSION: T1DM, with or without other concomitant autoimmune diseases, may increase the risk for severe OHSS. Awareness of the interaction of preexisting conditions and risk for vascular leak disorders is needed for comprehensive counseling prior to embarking on ovarian stimulation. Preventive measures may be important considerations in this population.

A retrospective cross-sectional study: fresh cycle endometrial thickness is a sensitive predictor of inadequate endometrial thickness in frozen embryo transfer cycles.

BACKGROUND: The purpose of this study is to assess predictors of inadequate endometrial cavity thickness (ECT), defined as < 8 mm, in frozen embryo transfer (FET) cycles. METHODS: This is a retrospective cross-sectional study at an academic fertility center including 274 women who underwent their first endometrial preparation with estradiol for autologous FET in our center from 2001-2009. Multivariable logistic regression was performed to determine predictors of inadequate endometrial development in FET cycles. RESULTS: Neither age nor duration of estrogen supplementation were associated with FET endometrial thickness. Lower body mass index, nulliparity, previous operative hysteroscopy and thinner fresh cycle endometrial lining were associated with inadequate endometrial thickness in FET cycles. A maximum thickness of 11.5 mm in a fresh cycle was 80% sensitive and 70% specific for inadequate frozen cycle thickness. CONCLUSIONS: Previous fresh cycle endometrial cavity thickness is associated with subsequent FET cycle endometrial cavity thickness. Women with a fresh cycle thickness of 11.5 mm or less may require additional intervention to achieve adequate endometrial thickness in preparation for a frozen cycle.

Risk of multiple gestation after ovulation induction in polycystic ovary syndrome.

OBJECTIVE: To compare the incidence of multiple gestation following treatment with clomiphene citrate (CC), metformin (MET) or gonadotropins in polycystic ovary syndrome (PCOS) patients undergoing ovulation induction. STUDY DESIGN: This was a retrospective, cohort study performed in an academic reproductive endocrine practice. PCOS patients presenting for first-trimester ultrasound were identified and assigned to 1 of 3 groups: CC-resistant patients who conceived after use of metformin +/- CC (group A), CC-resistant patients who conceived after gonadotropins (group B) and PCOS patients who conceived with CC only (group C). Multiple pregnancy outcome data were collected by chart review and patient interview. RESULTS: One hundred one pregnancies were identified in PCOS patients who had conceived after ovulation induction (OI). The rate of multiple gestation was higher in group B (36%) than in A (0%) or C (11%). CONCLUSION: The rate of multiple births was significantly lower with MET use during OI. Because multiple gestation is associated with higher complication rates and medical costs, our data offer an additional reason for use of MET for OI in PCOS patients who fail CC.

Risk of surgery after use of potassium chloride for treatment of tubal heterotopic pregnancy.

BACKGROUND: Spontaneous heterotopic pregnancies are rare, but with assisted reproductive techniques the incidence may approach 1:100. With the widespread use of transvaginal ultrasonography, physicians have attempted treatment of heterotopic pregnancies with minimally invasive procedures such as transvaginal guided potassium chloride (KCl) injection. However, there are few data on the success of this treatment. CASE: A 30-year-old primigravida presented with a desired pregnancy and was found to have a tubal pregnancy in addition to an intrauterine pregnancy. Ultrasound-guided KCl injection into the heterotopic pregnancy was complicated by abdominal pain, surgical abdomen, and hemoperitoneum requiring salpingectomy. CONCLUSION: A review of the literature revealed that 55% of tubal heterotopic pregnancies treated by KCl injection required subsequent salpingectomy. This raises concerns about the advisability of this treatment.

Radiographic and hysteroscopic findings of a placental site nodule.

OBJECTIVE: To report a case of placental site nodule discovered on hysterosalpingogram and evaluated by sonohysterography and hysteroscopy in a patient presenting with infertility. DESIGN: Case report. SETTING: Academic reproductive endocrinology center. PATIENT(S): A 30-year-old gravida 1 para 1 receiving evaluation for secondary infertility. INTERVENTION(S): Hysterosalpingogram, sonohysterography, and operative hysteroscopy with excision. MAIN OUTCOME MEASURE(S): Diagnosis and treatment of intrauterine lesion. RESULT(S): Pathology of the excisional biopsy from operative hysteroscopy revealed a placental site nodule. CONCLUSION(S): We report one of the first radiographic and hysteroscopic findings of a placental site nodule. This case demonstrates that in addition to the most common causes of uterine filling defects seen on hysterosalpingogram and sonohysterography, rarer lesions like placental site nodule also need to be considered in the differential diagnosis. Placental site nodule is a benign lesion that requires correct diagnosis to distinguish it from other more serious placental findings, but long-term follow-up is unnecessary. Therapy consists of diagnosis and expectant management.

Variability in the practice of fertility preservation for patients with cancer.

Fertility is important to women and men with cancer. While options for fertility preservation (FP) are available, knowledge regarding the medical application of FP is lacking. Therefore we examined FP practices for cancer patients among reproductive endocrinologists (REs). A 36 item survey was sent to board-certified REs. 98% of respondents reported counseling women with cancer about FP options. Oocyte and embryo cryopreservation were universally offered by these providers, but variability was noted in reported management of these cases-particularly for women with breast cancer. 86% of the respondents reported using letrozole during controlled ovarian stimulation (COS) in patients with estrogen receptor positive (ER+) breast cancer to minimize patient exposure to estrogen. 49% of respondents who reported using letrozole in COS for patients with ER+ breast cancer reported that they would also use letrozole in COS for women with ER negative breast cancer. Variability was also noted in the management of FP for men with cancer. 83% of participants reported counseling men about sperm banking with 22% recommending against banking for men previously exposed to chemotherapy. Overall, 79% of respondents reported knowledge of American Society for Clinical Oncology FP guidelines-knowledge that was associated with providers offering gonadal tissue cryopreservation (RR 1.82, 95% CI 1.14-2.90). These findings demonstrate that RE management of FP in cancer patients varies. Although some variability may be dictated by local resources, standardization of FP practices and communication with treating oncologists may help ensure consistent recommendations and outcomes for patients seeking FP.

Septate uterus with cervical duplication and longitudinal vaginal septum: a report of five new cases.

OBJECTIVE: To describe a unique congenital müllerian anomaly. DESIGN: Case report. SETTING: A university-based reproductive endocrine center. PATIENT(S): Five reproductive-age, nulligravida patients who underwent clinical, radiologic, and surgical work-up. INTERVENTION(S): Retrospective review of prior medical records and studies. MAIN OUTCOME MEASURE(S): Definition of abnormal pelvic anatomy. RESULT(S): Five patients from a university-based, reproductive endocrine center were found to have cervical duplication with a longitudinal vaginal septum, uterine septum, and a normal fundus. The patients most often presented initially to their primary obstetrician-gynecologists with symptomatic complaints secondary to their vaginal septums. Diagnoses were obtained with physical examinations, ultrasound imaging, hysterosalpingograms, magnetic resonance imaging, and surgical evaluation. CONCLUSION(S): These findings call into question the classic hypothesis of unidirectional (caudal to cranial) müllerian development and supports an alternative embryologic hypothesis of Müller et al., which states that fusion and resorption begins at the isthmus and proceeds simultaneously in both the cranial and caudad directions. The high number of cases reported here might be due to the increased accessibility and accuracy of such imaging modalities as magnetic resonance imaging. These patients will be followed longitudinally so that it can be determined whether this anomaly affects fertility and so that the optimal treatment plans can be developed.

The auto-amputated adnexa: a review of findings in a pediatric population.

STUDY OBJECTIVE: To quantify our experience and that of the literature with diagnosis and management of the auto-amputated adnexa in a pediatric population. DESIGN: Case series and literature review. SETTING: Tertiary care medical center. PARTICIPANTS: Case series of pediatric patients (<18 years of age) with surgically documented adnexal auto-amputation collected from our medical center and the literature. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Auto-amputated adnexa. RESULTS: In addition to the 3 cases discussed from our institution, 91 cases of auto-amputated adnexa were identified in the literature dating back to 1943, for a total of 94 cases. Forty-nine percent (46/94) of the cases involved girls in a pediatric population (<18 years of age). Of these, the majority (n = 26) were identified in a subgroup of girls who were diagnosed with an adnexal cyst by antenatal ultrasound. Most of these neonates were asymptomatic at birth or had a palpable abdominal mass (n = 6) and at the time of surgical exploration were found to have an auto-amputated adnexa. 34 out of 46 cases were analyzed in detail. The right adnexa were involved in 56% of the cases. The most common presenting complaint verbalized by the older girls was pain; however, 8 cases were identified in asymptomatic girls undergoing unrelated diagnostic testing. CONCLUSION: The auto-amputated adnexa is a rare finding in the pediatric population, but it must be considered as a possible explanation for the incidental finding of absence of the fallopian tube or ovary in the subgroup of patients who undergo surgery for any reason. Patients with an antecedent history of pelvic pain either chronic or intermittent in nature may be diagnosed with torsion or less frequently auto-amputation of the adnexa. A fetal "pelvic mass" or "ovarian cyst" may predispose the adnexa to torsion and subsequent auto-amputation either in-utero or post-delivery. Many of these antenatally diagnosed cysts and even subsequent auto-amputations are completely asymptomatic, however, and do not compromise fertility assuming the contralateral adnexa are normal. Thus expectant management is appropriate for small (less than 4 cm), asymptomatic simple cysts and even suspected auto-amputated adnexa in an asymptomatic patient.

Sperm banking for fertility preservation: a 20-year experience.

OBJECTIVE: Sperm banking is an effective method to preserve fertility, but is not universally offered to males facing gonadotoxic treatment in the United States. We compared the disposition and semen parameters of cryopreserved sperm from individuals referred for sperm banking secondary to a cancer diagnosis to those of sperm from men banking for infertility reasons. STUDY DESIGN: We performed a retrospective cohort study that reviewed 1118 records from males who presented to bank sperm at Washington University between 1991 and 2010. We collected and analyzed demographics, semen parameters, and disposition of banked sperm. RESULTS: Four hundred and twenty-three men with cancer and 348 banking for infertility reasons attempted sperm cryopreservation in our unit during the specified time period. The most prevalent cancers in our cohort were testicular (32%), lymphoma (25%), and leukemia (11%). Patients with leukemia had the lowest pre-thaw counts and motility. Most cancer patients (57%) who banked elected to use, transfer to another facility, or keep their specimens in storage. The remaining samples were discarded electively (34%) or following death (8%). Overall semen parameters were similar between the cancer and infertility groups, but demographics, ability to bank a sample, azoospermia rates, length of storage, current banking status, and use of banked sperm differed significantly between the two groups. CONCLUSIONS: The majority of cancer patients who banked survived their cancer and chose to continue storage of banked samples. Cancer patients were more likely than infertility patients to use or continue storage of banked samples. Our study provides evidence that sperm banking is a utilized modality of fertility preservation in patients with a myriad of cancer diagnoses and should be offered to all men facing gonadotoxic therapies. Further work is needed to determine where disparities in access to sperm banking exist to improve the potential for future fertility in these males.

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.

OBJECTIVE: To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. DESIGN: Prospective cohort study. SETTING: University in vitro fertilization (IVF) practice. PATIENT(S): A total of 102 women undergoing IVF. INTERVENTION(S): Measurement of FFAs in serum and ovarian follicular fluid. MAIN OUTCOME MEASURE(S): Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. RESULT(S): Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 µmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (ß=1.2; OR 3.4, 95% CI 1.1-10.4). CONCLUSION(S): Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility.

Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles.

To determine the impact of maternal metabolic state on oocyte development in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), we retrospectively analyzed a cohort of women with PCOS undergoing IVF/ICSI from 2008-2009 in a university-based fertility center. We determined that women with PCOS and obesity have smaller oocytes than control subjects, and that when further subdivided by body mass index, both PCOS and obesity independently influence oocyte size.

Smaller fetal size in singletons after infertility therapies: the influence of technology and the underlying infertility.

OBJECTIVE: To determine whether fetal size differences exist between matched fertile and infertile women and among women with infertility achieving pregnancy through various treatment modalities. DESIGN: Retrospective cohort study with propensity score analysis. SETTING: Tertiary care center and affiliated community hospitals. PATIENT(S): 1,246 fertile and 461 infertile healthy women with singleton livebirths over a 10-year period. INTERVENTION(S): Infertile women conceiving without medical assistance, with ovulation induction, or with in vitro fertilization. MAIN OUTCOME MEASURE(S): Birthweight; secondary outcomes included crown-rump length, second-trimester estimated fetal weight, and incidence of low birth weight and preterm delivery. RESULT(S): Compared with matched fertile women, infertile women had smaller neonates at birth (3,375 ± 21 vs. 3,231 ± 21 g) and more low-birth-weight infants (relative risk = 1.68, 95% confidence interval, 1.06, 2.67). Neonates conceived via ovulation induction were the smallest among the infertility subgroups compared with the neonates of fertile women (3,092 ± 46 vs. 3,397 ± 44 g). First-trimester fetal size was smaller in infertile versus fertile women (crown-rump length 7.9 ± 0.1 vs. 8.5 ± 0.1 mm). Within the infertility subgroups, no differences in fetal or neonatal size were found. CONCLUSION(S): The inherent pathologic processes associated with infertility may have a larger impact on fetal growth than infertility therapies.

A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization.

OBJECTIVE: To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP). DESIGN: Prospective, randomized, double-blinded, crossover study. SETTING: University-based infertility center. PATIENT(S): One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos. INTERVENTION(S): Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrode's solution. MAIN OUTCOME MEASURE(S): Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate. RESULT(S): Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy. CONCLUSION(S): In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. INTERVENTION(S): Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate. RESULT(S): Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). CONCLUSION(S): Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients.

Encouraging patient-driven single-embryo transfer.

Single-embryo transfer (SET) removes the risk of multiples in in vitro fertilization (IVF), but women with unfavorable IVF prognosis have been dissuaded from SET despite their desire to avoid multiples. In our clinic, 54% of the women who requested SET delivered healthy singletons, even though only two of them had met the American Society for Reproductive Medicine's SET guidelines. This demonstrates the value of encouraging patient-driven SET.