Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

RESEARCH QUESTIONS: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? DESIGN: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. RESULTS: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. CONCLUSIONS: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.

Postponing Childbearing and Fertility Preservation in Young Professional Women.

OBJECTIVES: To evaluate young women's awareness of ovarian reserve testing and oocyte cryopreservation (OC) and assess how testing ovarian reserve may affect the desire for fertility preservation. METHODS: Three questionnaire-based observational studies were conducted among female students/young professionals 20 years of age and older. The third survey was completed after participants were offered anti-Mullerian hormone (AMH) testing. The main outcomes measured included awareness that OC is available, interest in pursuing fertility preservation, and whether interest would change based on knowledge of declining fertility. RESULTS: The first tier of the study included a survey of a total of 337 women. The majority of female subjects were aware of OC (92.1%). Approximately 38.5% of the women responded that they would consider OC for future fertility purposes. This percentage increased to 60.3% if one was aware her fertility was declining. The second tier of the study included 42 resident/fellow physicians who were offered AMH testing. A survey was completed before and after testing was completed. Approximately 12% of participants stated that their AMH level altered their anticipated age of childbearing, whereas 24% would consider cryopreservation based on their results. The most common concern regarding OC was the cost. CONCLUSIONS: Women should be counseled regarding reproductive aging and options for fertility preservation. Offering ovarian reserve testing and making OC more affordable may increase the number of women who undergo elective OC.

Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Although a comorbidity of PCOS is obesity, many are lean. We hypothesized that increased saturated fat consumption and obesity would exacerbate metabolic and stress indices in a rodent model of PCOS. Female rats were implanted with the nonaromatizable androgen dihydrotestosterone (DHT) or placebo pellets prior to puberty. Half of each group was maintained ad libitum on either a high-fat diet (HFD; 40% butter fat calories) or nutrient-matched low-fat diet (LFD). Irrespective of diet, DHT-treated animals gained more body weight, had irregular cycles, and were glucose intolerant compared with controls on both diets. HFD/DHT animals had the highest levels of fat mass and insulin resistance. DHT animals demonstrated increased anxiety-related behavior in the elevated plus maze by decreased distance traveled and time in the open arms. HFD consumption increased immobility during the forced-swim test. DHT treatment suppressed diurnal corticosterone measurements in both diet groups. In parallel, DHT treatment significantly dampened stress responsivity to a mild stressor. Brains of DHT animals showed attenuated c-Fos activation in the ventromedial hypothalamus and arcuate nucleus; irrespective of DHT-treatment, however, all HFD animals had elevated hypothalamic paraventricular nucleus c-Fos activation. Whereas hyperandrogenism drives overall body weight gain, glucose intolerance, anxiety behaviors, and stress responsivity, HFD consumption exacerbates the effect of androgens on adiposity, insulin resistance, and depressive behaviors.

Weight loss by calorie restriction versus bariatric surgery differentially regulates the hypothalamo-pituitary-adrenocortical axis in male rats.

Behavioral modifications for the treatment of obesity, including caloric restriction, have notoriously low long-term success rates relative to bariatric weight-loss surgery. The reasons for the difference in sustained weight loss are not clear. One possibility is that caloric restriction alone activates the stress-responsive hypothalamo-pituitary-adrenocortical (HPA) axis, undermining the long-term maintenance of weight loss, and that this is abrogated after bariatric surgery. Accordingly, we compared the HPA response to weight loss in five groups of male rats: (1) high-fat diet-induced obese (DIO) rats treated with Roux-en-Y gastric bypass surgery (RYGB, n = 7), (2) DIO rats treated with vertical sleeve gastrectomy (VSG, n = 11), (3) DIO rats given sham surgery and subsequently restricted to the food intake of the VSG/RYGB groups (Pair-fed, n = 11), (4) ad libitum-fed DIO rats given sham surgery (Obese, n = 11) and (5) ad libitum chow-fed rats given sham surgery (Lean, n = 12). Compared with Lean controls, food-restricted rats exhibited elevated morning (nadir) non-stress plasma corticosterone concentration and increased hypothalamic corticotropin-releasing hormone and vasopressin mRNA expression, indicative of basal HPA activation. This was largely prevented when weight loss was achieved by bariatric surgery. DIO increased HPA activation by acute (novel environment) stress and this was diminished by bariatric surgery-, but not pair-feeding-, induced weight loss. These results indicate that the HPA axis is differentially affected by weight loss from caloric restriction versus bariatric surgery, and this may contribute to the differing long-term effectiveness of these two weight-loss approaches.

Metabolic, behavioral, and reproductive effects of vertical sleeve gastrectomy in an obese rat model of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Its clinical expression is diverse, including metabolic, behavioral, and reproductive effects, with many affected by obesity and decreased quality of life. Women with PCOS who have undergone surgically induced weight loss have reported tremendous benefit, not only with weight loss, but also improvement of hyperandrogenism and menstrual cyclicity. METHODS: In a rat model of PCOS achieved via chronic administration of dihydrotestosterone (DHT) exposure, we investigated the ability of bariatric surgery, specifically vertical sleeve gastrectomy (VSG), to ameliorate the metabolic, behavioral, and reproductive abnormalities invoked by this PCOS model. RESULTS: We found that DHT treatment combined with exposure to a high-fat diet resulted in increased body weight and body fat, impaired fasting glucose, hirsutism, anxiety, and irregular cycles. VSG resulted in reduced food intake, body weight, and adiposity with improved fasting glucose and triglycerides. VSG induced lower basal corticosterone levels and attenuated stress responsivity. Once the DHT levels decreased to normal, regular estrous cyclicity was also restored. CONCLUSIONS: VSG, therefore, improved PCOS manifestations in a comprehensive manner and may represent a potential therapeutic approach for specific aspects of PCOS.

Hysteroscopic enucleation of type II submucosal uterine leiomyomas using a TRUCLEAR hysteroscopic morcellator: case report and review of the literature.

OBJECTIVE: We describe a case of complete enucleation of a Type II leiomyoma using the TRUCLEAR™ (Smith & Nephew Endoscopy, Andover, MA) hysteroscopic morcellator (THM) and demonstrate appropriate preoperative assessment and intraoperative surgical principles during this case. Complete hysteroscopic enucleation of Type II leiomyomas is also systematically reviewed. MATERIALS AND METHODS: In this case report and review, performed in a tertiary-care university setting, the THM was used for hysteroscopic resection of two submucosal leiomyomas. RESULTS: A 41-year-old gravida 1 para 0010 presented with infertility and symptomatic leiomyomas. Preoperative assessment included a hysterosalpingogram, magnetic resonance imaging, and sonohysterography demonstrating several extrinsic impressions on the uterine cavity and two submucosal leiomyomas (Type I and Type II). Diagnostic hysteroscopy confirmed findings. As the THM blade started resecting the Type II leiomyoma, it began to separate from the underlying myometrium. Attempts to release the edge of the leiomyoma, including reverse rotation of the blade, completely enucleated the leiomyoma, which was subsequently removed from the cavity with the THM. Minimal bleeding was encountered; intraoperative ultrasound confirmed normal overlying myometrium. Postoperatively, sonohysterography showed complete closure of the dead space with only a slightly distorted endometrial cavity. CONCLUSIONS: Hysteroscopic uterine leiomyoma enucleation should only be performed in experienced hands. Inadvertent enucleation of a Type II leiomyoma with a THM device is described, with review of key surgical principles that guided safe resection.

Effects of embryo transfer catheters on the endometrial surface noted at hysteroscopy.

STUDY OBJECTIVE: To assess the effects on the endometrial surface of embryo transfer catheters using hysteroscopy with ultrasound guidance. DESIGN: Prospective descriptive study (Canadian Task Force classification III). SETTING: University-based clinical practice. PATIENTS: Twenty patients with a documented difficult trial transfer (TT). INTERVENTION: All patients underwent an intraoperative TT using an Edwards-Wallace catheter (n = 10), a Soft-Pass catheter with obturator (n = 2), or an Echosight Patton catheter with a coaxial wire (n = 8), with placement assured using ultrasound. This was followed by hysteroscopy and cervical surgical correction. MEASUREMENTS AND MAIN RESULTS: A 5-mm hysteroscope was used to visualize, assess, and document TT catheter placement and effects on the endometrial cavity. The Wallace catheter caused the least trauma (20%). The Soft-Pass catheter with obturator (100%) resulted in linear grooves in the endometrial surface. The most traumatic effects occurred with use of the coaxial catheter (38%), which caused shaving with petechial bleeding past the point of obstruction. In addition, 3 of the Wallace catheters were improperly placed (cannulation of tubal ostia, n = 2) and coiled back (n =1). CONCLUSION: Despite ultrasound guidance, endometrial disruption and catheter displacement occurs with difficult embryo transfer catheter placement, which may suggest an explanation for lower pregnancy rates in these difficult cases. Greater attention to correction of cervical disease before an in vitro fertilization-embryo transfer cycle may improve clinical outcomes.

Continued parental attendance at a clinic for adult survivors of childhood cancer.

PURPOSE: Adult survivors of childhood cancer have been an underserved and understudied population. Few clinics are available to take care of them, unlike the numerous ones that exist for children. The authors established a clinic that would take care of all survivors diagnosed before the age of 25 years, ensuring the participation of a significant number of adults. The authors observed that many adult patients came to their annual visits accompanied by one or both of their parents. The rate was almost three times as high compared with parents in either a primary care or subspecialty internal medicine clinic. METHODS: The authors investigated this phenomenon by asking parents of adult survivors to fill out a questionnaire that collected demographic information as well as reasons for parents accompanying their adult children to doctors' appointments. Open-ended comments were also solicited. RESULTS: Most parents who came with their adult survivor children did not accompany their other children to doctor visits and commented that they felt there was a unique bond created by the cancer experience that did not diminish with increasing age of their children. The rate of parental attendance was independent of diagnosis or demographic indicators. Many parents stated that they continued to be concerned about their child's diagnosis, overall health, and risk for cancer recurrence. DISCUSSION: Parents of adult survivors of childhood cancer may harbor deep feelings of protectiveness that continue well beyond the initial treatment and off-treatment periods when the threat of primary cancer recurrence is a realistic concern. This can be manifested in them by accompanying their adult children to doctors' appointments and deserves further study.