Intrauterine insemination cycles: prediction of success and thresholds for poor prognosis and futile care.

PURPOSE: We aimed to define intrauterine insemination (IUI) cycle characteristics associated with viable birth, identify thresholds below which IUI treatments are consistent with very poor prognosis and futile care, and develop a nomogram for individualized application. METHODS: This retrospective cohort study evaluated couples using fresh partner ejaculate for IUI from January 2005 to September 2017. Variables included female age, semen characteristics, and ovarian stimulation type. Using cycle-level data, we evaluated the association of these characteristics with the probability of viable birth by fitting generalized regression models for a binary outcome with a logit link function, using generalized estimating equation methodology to account for the correlation between cycles involving the same patient. RESULTS: The cohort consisted of 1117 women with 2912 IUI cycles; viable birth was achieved in 275 (9.4%) cycles. Futile care (viable birth rate < 1%) was identified for women age > 43, regardless of stimulation type or inseminate motility (IM). Very poor prognosis (viable birth rate < 5%) was identified for women using oral medications or Clomid plus gonadotropins who were (1) age < 35 with IM < 49%, (2) age 35-37 with IM < 56%, or (3) age ≥ 38, and (4) women age ≥ 38 using gonadotropins only with IM < 60%. A clinical prediction model and nomogram was developed with an optimism-corrected c-statistic of 0.611. CONCLUSIONS: The present study highlights the impact of multiple clinical factors on IUI success, identifies criteria consistent with very poor prognosis and futile care, and provides a nomogram to individualize counseling regarding the probability of a viable birth.

Fertility Preservation Outcomes in Adolescent and Young Adult Feminizing Transgender Patients.

BACKGROUND: Fertility preservation enables patients undergoing gonadotoxic therapies to retain the potential for biological children and now has broader implications in the care of transgender individuals. Multiple medical societies recommend counseling on fertility preservation before initiating therapy for gender dysphoria; however, outcome data pre- and posttreatment are limited in feminizing transgender adolescents and young adults. METHODS: The University of Pittsburgh Institutional Research Board approved this study. Data were collected retrospectively on transgender patients seeking fertility preservation between 2015 and 2018, including age at initial consultation and semen analysis parameters. RESULTS: Eleven feminizing transgender patients accepted a referral for fertility preservation during this time; consultation occurred at median age 19 (range 16-24 years). Ten patients attempted and completed at least 1 semen collection. Eight patients cryopreserved semen before initiating treatment. Of those patients, all exhibited low morphology with otherwise normal median semen analysis parameters. In 1 patient who discontinued leuprolide acetate to attempt fertility preservation, transient azoospermia of 5 months' duration was demonstrated with subsequent recovery of spermatogenesis. In a patient who had previously been treated with spironolactone and estradiol, semen analysis revealed persistent azoospermia for the 4 months leading up to orchiectomy after discontinuation of both medications. CONCLUSIONS: Semen cryopreservation is a viable method of fertility preservation in adolescent and young adult transgender individuals and can be considered in patients who have already initiated therapy for gender dysphoria. Further research is needed to determine the optimal length of time these therapies should be discontinued to facilitate successful semen cryopreservation.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1-7] vs 1 [1-4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6-14] vs 4 [2-7]; P < .001; days until return to normal, 15 [10-29] vs 10 [10-15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.