Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial.

BACKGROUND: Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth. METHODS AND FINDINGS: In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful. CONCLUSIONS: A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02432209.

Reservoir induced bladder rupture: a complication of inflatable penile prosthesis revision surgery.

Reservoir induced bladder rupture is a rare complication of inflatable penile prosthesis (IPP) revision surgery. Our aim is to review the literature and describe our experience with this complication using two case reports that involved reusing an in-situ reservoir. In each case, an episode of gross hematuria indicated that a bladder rupture had occurred. From our experience, we propose ways to possibly avoid and if necessary, manage this rare complication.

Intrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial.

STUDY QUESTION: Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility? SUMMARY ANSWER: Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success. WHAT IS ALREADY KNOWN: We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome. STUDY DESIGN, SIZE, DURATION: This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%). LIMITATIONS, REASONS FOR CAUTION: This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI. WIDER IMPLICATIONS OF THE FINDINGS: Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI. STUDY FUNDING/COMPETING INTEREST(S): Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work. TRIAL REGISTRATION NUMBER: n/a.

Defining hypogonadism in male partners of couples with unexplained infertility.

INTRODUCTION: Men with unexplained infertility (UI) should undergo an initial hormonal evaluation including serum FSH and total testosterone (TT). Unfortunately, there is no consensus regarding which TT cut point should be used to define hypogonadism in such men. To determine the best definition for hypogonadism, three different, literature-based TT cut points were used to assess associations between TT and semen parameters. The hypothesis was that the lowest TT cut point would associate with poorest sperm parameters. MATERIALS AND METHODS: We performed an IRB-approved retrospective chart review of 247 consecutive males presenting for evaluation of male factor infertility. After exclusions, basic statistics and correlation analysis of semen analysis parameters, TT, age, and body mass index (BMI) were evaluated on 128 men (age 34+/-33.5) categorized by three different TT cut points: 65 males were hypogonadal according to a TT cutoff of < 264; 16 with a cutoff of 264-300; 44 with a cutoff of 301-400; and 42 with a TT over 400 ng/dL. Basic statistics, one-way ANOVA and Levene comparative analysis were performed. Besides a negative correlation between TT and BMI, there was no significant association between the three TT literature-based cut points and the other studied parameters. These findings were further supported by multiple comparison analyses. RESULTS: For men with UI, regardless of how hypogonadism was defined, no relationship between semen parameters and TT was found. CONCLUSION: Conventional, TT-based definitions of male hypogonadism in the setting of UI need to be clarified. Clinically relevant, accurate and reproducible multivariable biomarkers need to be investigated to further advance best practices for treating men with UI.

Fertility Related Quality of Life, Gonadal Function and Erectile Dysfunction in Male Partners of Couples with Unexplained Infertility.

PURPOSE: We sought to determine whether lower fertility related quality of life or depression in men of couples with unexplained infertility is associated with low total testosterone levels, abnormal semen quality or erectile dysfunction. MATERIALS AND METHODS: This study is a secondary analysis of a large, multicenter, randomized controlled trial in couples with unexplained infertility. Male partners underwent baseline semen analysis with measurement of fasting total testosterone and gonadotropin. They also completed surveys, including the FertiQOL (Fertility Quality of Life), the PHQ-9 (Patient Health Questionnaire-9) and the IIEF (International Index of Erectile Function). The primary study outcomes were total testosterone with low total testosterone defined as less than 264 ng/dl, semen parameters and the IIEF score. We performed multivariable logistic regression analyses adjusted for patient age, race, body mass index, education, smoking, alcohol use, infertility duration and comorbidity. RESULTS: A total of 708 men with a mean ± SD age of 34.2 ± 5.6 were included in study. Of the men 59 (8.3%) had a PHQ-9 score of 5 or greater, which was consistent with depression, 99 (14.0%) had low total testosterone and 63 (9.0%) had mild or worse erectile dysfunction. Neither the FertiQOL score nor depression was associated with total testosterone or any semen parameter. The FertiQOL score was inversely associated with erectile dysfunction (for every 5-point score decline AOR 1.30, 95% CI 1.16-1.46). Depressed men were significantly more likely to have erectile dysfunction than nondepressed men (AOR 6.31, 95% CI 3.12-12.77). CONCLUSIONS: In men in couples with unexplained infertility lower fertility related quality of life and depression are strongly associated with erectile dysfunction. However, neither is associated with spermatogenesis or testosterone levels. Erectile dysfunction in infertile men merits longitudinal investigation in future studies.

The efficiency of single institutional review board review in National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network-initiated clinical trials.

BACKGROUND/AIMS: Timely review of research protocols by institutional review boards leads to more rapid initiation of clinical trials, which is critical to expeditious translation from bench to bedside. This observational study examined the impact of a single institutional review board on time and efforts required to initiate clinical trials by the National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. METHODS: Collection of data from the same six main clinical sites for three current clinical trials and two past clinical trials, including time from institutional review board submission to approval, pages submitted, consent form length, number of required attachments, other regulatory requirements, order of review at central or local sites, and language in documents at individual participating sites. Results from two past clinical trials were also included. RESULTS: While time required for actual institutional review board submission's review and initial approval was reduced with use of a single institutional review board for multicenter trials (from a mean of 66.7-24.0 days), total time was increased (to a mean of 111.2 or 123.3 days). In addition to single institutional review board approval, all institutions required local approval of some components (commonly consent language and use of local language), which varied considerably. The single institutional review board relied on local institutions for adding or removing personnel, conflict of interest review, and auditing of activities. CONCLUSION: A single institutional review board reduced time for initial review and approval of protocols and informed consents, although time for the entire process was increased, as individual institutions retained oversight of components of required regulatory review. In order to best achieve the National Institute of Health's goals for improved efficiency in initiation and conduct of multisite clinical research, greater coordination with local institutional review boards is key to streamlining and accelerating initiation of multisite clinical research.

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

BACKGROUND: The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. METHODS: We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. RESULTS: After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. CONCLUSIONS: In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.

BACKGROUND: Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes. METHODS: In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period. RESULTS: Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups. CONCLUSIONS: As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).

Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

BACKGROUND: While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. OBJECTIVE: The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. STUDY DESIGN: A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. RESULTS: Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. CONCLUSION: Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function.

Experiences and characteristics of women seeking and completing at-home medical termination of pregnancy through online telemedicine in Ireland and Northern Ireland: a population-based analysis.

OBJECTIVE: To examine the characteristics and experiences of women in Ireland and Northern Ireland seeking at-home medical termination of pregnancy (TOP) using online telemedicine. DESIGN: Population-based study. SETTING: Ireland and Northern Ireland. POPULATION: Between 1 January 2010 and 31 December 2015, 5650 women requested at-home medical TOP through online telemedicine initiative Women on Web. METHODS: We examined the demographics and circumstances of women requesting medical TOP and examined the experiences of the 1023 women who completed TOP between January 2010 and December 2012. We conducted a content analysis of women's evaluations and used logistic regression to examine factors associated with lack of emotional support during and after TOP MAIN OUTCOME MEASURES: Satisfaction with TOP; feelings before and after TOP; emotional support during TOP. RESULTS: Women requesting TOP were diverse with respect to age, pregnancy circumstances and reasons for seeking TOP. Among those completing TOP, 97% felt they made the right choice and 98% would recommend it to others in a similar situation. Women commonly reported serious mental stress caused by their pregnancies and their inability to afford travel abroad to access TOP. The feelings women most commonly reported after completing TOP were 'relieved' (70%) and 'satisfied' (36%). Women with financial hardship had twice the risk of lacking emotional support (odds ratio = 2.0, P < 0.001). CONCLUSIONS: The vast majority of women who completed at-home medical TOP through Women on Web had a positive experience. These demonstrated benefits to health and wellbeing contribute new evidence to the debate surrounding abortion laws in Ireland and Northern Ireland. TWEETABLE ABSTRACT: Irish and Northern Irish women completing at-home medical TOP report benefits for health, wellbeing and autonomy.

Contraceptive method preferences and provision after termination of pregnancy: a population-based analysis of women obtaining care with the British Pregnancy Advisory Service.

OBJECTIVE: To examine contraceptive choices among women seeking termination of pregnancy (TOP) and the provision of the chosen methods. DESIGN: Population-based study. SETTING: British Pregnancy Advisory Service (BPAS) clinics in England and Wales. POPULATION: Between 1 January 2011 and 31 December 2014, 211 215 women had a TOP at BPAS, were offered contraceptive counselling, and were eligible to obtain contraception at no cost. METHODS: We examined electronic records from BPAS and assessed the proportions of women who accepted contraceptive counselling and chose a contraceptive method, as well as the distributions of methods chosen, analysed by provider and by TOP type. We calculated the proportions receiving their chosen method and the methods chosen by women using no method at conception. We used logistic regression to examine the factors associated with choice of an intrauterine contraceptive (IUC) or implant. MAIN OUTCOME MEASURES: Post-TOP contraceptive method choice. Receipt of chosen method post-TOP. RESULTS: Eighty-five per cent of women accepted contraceptive counselling and 51% chose to obtain a method from BPAS rather than from a GP or contraception and sexual health clinic post-TOP. [correction added on 25 November 2016 after first online publication: 51% has been inserted in the preceding sentence.] Among those who wanted to receive contraception from BPAS, 51% chose an IUC or implant and 19% chose oral contraceptives. Ninety-one per cent of women who obtained contraception from BPAS received their chosen method. Women were more likely to choose an IUC or implant if they obtained contraception from BPAS, had a surgical TOP, were parous, young, white, or had one or more previous TOPs. CONCLUSIONS: The standards set for patient-centred TOP care should emphasise the need for a full range of contraceptive options to be offered and provided post-TOP. TWEETABLE ABSTRACT: Uptake targets for long-acting reversible methods do not reflect women's post-TOP contraceptive preferences.

Fertility-related quality of life from two RCT cohorts with infertility: unexplained infertility and polycystic ovary syndrome.

STUDY QUESTION: Does fertility-related quality of life (FertiQOL) differ by infertility diagnosis between women with polycystic ovary syndrome (PCOS) and their partners, compared with couples with unexplained infertility (UI)? SUMMARY ANSWER: Women with PCOS report lower QOL than those with UI, whereas males with UI report lower QOL than males with PCOS partners. WHAT IS KNOWN ALREADY: The fertility-specific QOL survey, FertiQOL, has been used to examine fertility-related QOL in a number of worldwide cohorts. Few data have addressed fertility-related QOL as a function of infertility diagnosis. Overall, men report better QOL than women with infertility, and there is variation in FertiQOL scores across different samples from different countries. STUDY DESIGN, SIZE, DURATION: This was a prospective, cohort study derived from two concurrent, randomized clinical trials, and designed to examine QOL in infertile females with PCOS and UI at the time of enrollment compared with each other and their male partners; to compare concordance FertiQOL scores in this study across other worldwide cohorts; and to determine if baseline FertiQOL was associated with pregnancy outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS and their partners (n = 733 and n = 641, respectively), and couples with UI (n = 865 women and 849 men) completed a validated fertility-specific QOL survey (FertiQOL) at the time of the study screening visit. PCOS women were randomized to either clomiphene citrate or letrozole treatment; couples with UI were randomized to clomiphene citrate, letrozole or gonadotrophin plus IUI. FertiQOL results were compiled by diagnosis (PCOS or UI) and compared by diagnosis and sex using Wilcoxon Rank-Sum testing. Relationships between baseline FertiQOL and pregnancy outcomes were examined using logistic regression. Multivariable models were performed to assess the association between FertiQOL scores and key participant characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS had lower total FertiQOL scores (72.3 ± 14.8) than those with UI (77.1 ± 12.8; P < 0.001); this was true for each domain (except Relational). These differences were largely explained by variation in BMI, hirsutism, household income and age. Women had lower overall FertiQOL scores than their male partners. Males with PCOS partners had higher scores than males with UI (84.9 ± 10.2 versus 83.3 ± 10.8; P = 0.003). Scores were not consistently associated with conception or pregnancy outcome. LIMITATIONS, REASONS FOR CAUTION: The use of multiple tests of association may have resulted in spurious statistically significant findings. Inherent sociodemographic differences between women with PCOS and those with UI largely account for the lower QOL in women with PCOS. Our study was unable to assess if changes in QOL affected pregnancy outcome as FertiQOL data were collected prior to treatment. Finally, the participants for both studies represent their local communities, but are not a population-based sample and thus firm conclusions about how representative these couples are to the general population must be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS with elevated BMI and hirsutism scores and with lower socioeconomic status may require more, targeted psychosocial support than those with other diagnoses. Possible attribution of infertility to the male partner appears to result in a lower QOL. There appears to be substantial national variation in FertiQOL scores, with US-based cohorts reporting overall higher QOL. STUDY FUNDING/COMPETING INTERESTS: This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD39005 (to M.D.), U10 HD38992 (to R.S.L.), (to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), HD055944 (to P.C.), U10 HD055936 (to G.C.), U10HD055925 (to H.Z.); and U10 U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core of the Specialized Cooperative Centers Program in Reproduction and Infertility Research). Most importantly, this research was made possible by the funding by American Recovery and Reinvestment Act. N.S., E.E., J.C.T., C.G., H.H., R.A., P.C., G.C., C.C., M.D., S.J., W.D.S. and H.Z. report no conflicts of interests/disclosures. L.B.C. reports research support from Ferring Pharmaceuticals and Roche Diagnostics; R.S.L. reports receipt of consulting fees from AstraZeneca, Euroscreen, Sprout Pharmaceuticals, Taken, Kindex, Clarus and Bayer, Inc., and research support from AstraZeneca and Ferring Pharmaceuticals. R.D.R. reports research support from AbbVie. TRIAL REGISTRATION NUMBER: Pregnancy in Polycystic Ovary Syndrome II (PPCOS II), NCT00719186; Assessment of Multiple Intrauterine Gestations in Ovulation Stimulation (AMIGOS) NCT01044862, clinicaltrials.gov. TRIAL REGISTRATION DATE: PPCOS II 17 July 2008; AMIGOS 7 January 2010. DATE OF FIRST PATIENT'S ENROLMENT: PPCOS II 19 February 2009; AMIGOS 2 August 2010.

Retroperitoneal fluid collection following anterior spine surgery--differential and management.

Iatrogenic ureteral injuries are rare and must be accurately identified to minimizing the risk for additional complications. Anterior lumbar interbody fusion (ALIF) is a valuable technique utilized in spine surgery, with its own unique set of complications. For example, retroperitoneal fluid collections, following ALIF surgery are rare and may result in back pain, radicular pain, nausea, and even death. It is important to rapidly identify the nature of the fluid collection to clarify appropriate management options. The purpose of this case report is to present a differential diagnosis for a delayed presentation of an extremely large retroperitoneal fluid collection following anterior lumbar surgery, as well as to provide discussion on this rare complication. Specifically, a 51-year-old female with a history of numerous previous abdominal surgeries underwent an L3-S1 ALIF through a paramedian retroperitoneal approach. Postoperatively, she developed a large retroperitoneal fluid collection heralded by unilateral left lower extremity swelling and paresthesias. Fluid aspiration suggested a urine leak, but no specific injury was identified on retrograde pyelogram, most likely due to hardware obscuration in the area of presumed injury. A presumptive ureteral injury resulted in a ureteral stent placement, with resolution of the fluid collection and hydronephrosis. A high index of suspicion allowed for proper treatment, healing, and ultimately, a satisfactory outcome.

Repetitive percutaneous epididymal sperm aspirations (PESA's) resulted in asthenospermia and significant inflammation.

INTRODUCTION: In obstructive azoospermia, choosing a sperm retrieval method for intracytoplasmic sperm injection (ICSI) depends on the preference and expertise of both the urologist and the reproductive endocrinologist. Generally, a percutaneous epididymal sperm aspiration (PESA) is attempted first. Not uncommonly, multiple PESA's are necessary. This study utilizes a rat model to provide an understanding of sperm parameter and histological changes resulting from repetitive PESA procedures. MATERIALS AND METHODS: A cohort of 30 male Wistar rats of reproductive age (68-73 days) was divided into three groups of 10 (G1-G3). All three groups underwent a left epididymal head PESA using a 253/8 gauge needle. The untouched right epididymis acted as the control. At 14 day intervals, G2 and G3 underwent a second and third PESA respectively. Fourteen days after the final PESA, both epididymides and a 1 cm segment of both vas deferentia were harvested for sperm and histological evaluations. RESULTS: The percentage of vas specimens with a sperm count ≥ 5 x104/cc was 100%, 22%, and 20% for the G1, G2, G3 PESA samples respectively. Moreover, the percentage of the vas specimens with sperm motility ≥ 10% was 90%, 22%, and 20%, respectively. Epididymal granulomas were not seen in the control side, but formed in 70%, 100%, and 80% of G1, G2, G3 PESA specimens, respectively. CONCLUSIONS: In a rat model, PESA resulted in significant epididymal inflammation and a reduction in both sperm concentration and motility.

Effect of prospectively measured pregnancy intentions on the consistency of contraceptive use among young women in Michigan.

STUDY QUESTION: What is the predictive value of pregnancy intentions on contraceptive behaviours among women aged 18-19? SUMMARY ANSWER: Women aged 18-19 have high levels of inconsistent use of contraception, which mostly occur at times when women strongly wish to avoid a pregnancy. WHAT IS KNOWN ALREADY: Pregnancy intentions provide an indication of how well individuals achieve their reproductive goals. However, retrospective accounts of pregnancy intentions using dichotomous indicators suffer temporal instability and fail to capture the wide range of attitudes towards pregnancy. STUDY DESIGN, SIZE, DURATION: In this study, data are drawn from a population-based survey of 992 women of ages 18-19 years in Michigan, who completed weekly journals assessing contraceptive use, pregnancy intentions and reproductive outcomes during 2.5 years of follow-up. The response rate was 86% for the baseline interview and 65% after 2.5 years of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: We examined 15 446 pairs of journal entries. We used logistic regression with random effects to assess the predictive effect of women's desire to become pregnant and to avoid a pregnancy, measured each week, on consistency of use of contraception the following week. MAIN RESULTS AND THE ROLE OF CHANCE: Women reported inconsistent use of contraception in more than a quarter of weekly journals (28.3%). Consistent use of contraception increased from 22 to 78% as women s intentions to become pregnant decreased and increased from 23 to 78% as motivations to avoid pregnancy increased. The combination of scores of the pregnancy desire and avoidance scales shows indifferent or ambivalent pregnancy attitudes in 8.6% of weekly records. These women were more likely to report inconsistent contraceptive use compared with women who expressed anti-conception attitudes [OR = 2.8 (2.2-3.5)]. However, 23% of women who had unequivocal anti-conception feelings did not use contraception consistently, contributing to 72% of the weeks of inconsistent use in our population. LIMITATIONS, REASONS FOR CAUTION: In this study, consistency of contraceptive use, based on the use of contraception at every act of intercourse, does not fully capture a women's risk of becoming pregnant. The 35% attrition after 2.5 years may have affected the internal validity of our results, although a reanalysis based on the first year of observation produced very similar results. WIDER IMPLICATIONS OF THE FINDINGS: Because most instances of inconsistent use of contraception occur among women who are keen to avoid a pregnancy, our results suggest there is room for improving contraceptive behaviours by promoting use of methods which do not require user adherence. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institute of Child Health and Human Development for grant #R01-HDHD050329 (P.I. Barber, University of Michigan) and grant #R24HD047879 (Center infrastructure of the Office of Population Research at Princeton University, JT and KSH). None of the authors have a competing interest.

Biomarkers of Stress and Male Fertility.

To study if stress, as measured by salivary alpha-amylase and cortisol, negatively impacts male fertility, as measured by semen parameters, pregnancy, and live birth rates. Prospective, cohort study of men enrolled in the Males, Antioxidants, and Infertility (MOXI) trial. One-hundred twelve infertile men provided first-morning salivary and semen samples at baseline. Salivary samples were analyzed for alpha-amylase and cortisol. Couples attempted to conceive naturally (months 1-3) and with clomiphene citrate/intrauterine insemination (months 4-6). The association between stress-related biomarkers and semen parameters including DNA fragmentation was assessed using linear regression models adjusting for male age. Salivary levels were dichotomized at the 80th percentile. Pregnancy/live birth rates in couples in the upper quintile were compared to remaining subjects using chi-square testing. Salivary levels of alpha-amylase were not associated with semen parameters or DNA fragmentation. Salivary cortisol levels were not correlated with DNA fragmentation or normal morphology. For every 1-unit increase in salivary cortisol, total sperm count increased by 13.9 million (95% CI: 2.5, 25.3) and total motile sperm count increased by 9.9 million (95% CI: 3.2-16.6). Couple pregnancy rates and live birth rates did not differ for males in the highest quintile of alpha-amylase (27% and 28%, p = 0.96; 23% and 21%, p = 0.87) or cortisol (40% and 26%, p = 0.22; 35% and 19%, p = 0.12), compared to males with lower values. Physiologic measures of high stress may not harm but actually improve semen parameters among men with male-factor infertility.

Anatomical and histological equivalence of the human, canine, and bull vas deferens.

INTRODUCTION: Several animal models have been utilized for in-vitro experimentation and surgical training exercises of the vas deferens. The canine model is currently the standard for both in-vivo and ex-vivo study. Due to increasing costs associated with experimentation on canines, and in keeping with the principles of refine, reduce, and replace, a novel model that is cost-effective and easily obtained is desired. We compared morphology of the bull vas deferens to that of the human and the canine. MATERIALS AND METHODS: Bilateral vas deferens tissue from the human (n = 6), canine (n = 6), and bull (n = 5) were compared. Outer diameter (OD), inner diameter (ID), and microscopic measurements of the luminal mucosa and muscularis were then determined from each of these tissues. Histological comparisons were performed by a single pathologist. Data was analyzed using Two One-sided Tests (TOST) Analysis of Equivalence. RESULTS: According to the TOST statistical analysis, the vassal ID was equivalent for all three species. Similarly, equivalent microscopic measurements were noted for both vassal mucosal (human-canine and human-bull) and muscularis thicknesses (canine-bull). Lastly, all three species had similar histological characteristics. CONCLUSIONS: The vas deferens' of the human, canine, and bull are equivalent in many ways, including histological similarities. It is reasonable to conclude that the bull vas could be substituted for the human vas for both in-vitro testing and microscopic vasovasostomy simulation exercises. Specimens are cost-effective, provide ample tissue length, and are easy to obtain.

Male vitamin D status and male factor infertility.

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.