Zika Virus Causes Acute Infection and Inflammation in the Ovary of Mice Without Apparent Defects in Fertility.

BACKGROUND: Zika virus (ZIKV) has become a global concern because infection of pregnant mothers was linked to congenital birth defects. Zika virus is unique from other flaviviruses, because it is transmitted vertically and sexually in addition to by mosquito vectors. Prior studies in mice, nonhuman primates, and humans have shown that ZIKV targets the testis in males, resulting in persistent infection and oligospermia. However, its effects on the corresponding female gonads have not been evaluated. METHODS: In this study, we assessed the effects of ZIKV on the ovary in nonpregnant mice. RESULTS: During the acute phase, ZIKV productively infected the ovary causing accumulation of CD4+ and virus-specific CD8+ T cells. T cells protected against ZIKV infection in the ovary, as higher viral burden was measured in CD8-/- and TCRßδ-/- mice. Increased cell death and tissue inflammation in the ovary was observed during the acute phase of infection, but this normalized over time. CONCLUSIONS: In contrast to that observed with males, minimal persistence and no long-term consequences of ZIKV infection on ovarian follicular reserve or fertility were demonstrated in this model. Thus, although ZIKV replicates in cells of the ovary and causes acute oophoritis, there is rapid resolution and no long-term effects on fertility, at least in mice.

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.

Social media in the REI clinic: what do patients want?

PURPOSE: To elicit patient preferences for social media utilization and content in the infertility clinic. METHODS: This was a cross-sectional survey study conducted in three US fertility practices. Women presenting to the infertility clinic for an initial or return visit were offered an anonymous voluntary social media survey. The survey elicited patient perception of whether social media use in the infertility clinic is beneficial, and preferences regarding topics of interest. RESULTS: A total of 244 surveys were collected during the study period, of which 54.5% were complete. Instagram is a more popular platform than Twitter across all age groups. Use of both platforms varies by age, with patients ≥ 40 less likely to be active users. The majority of respondents felt that social media provided benefit to the patient experience in the infertility clinic (79.9%). "Education regarding infertility testing and treatment" and "Myths and Facts about infertility" were the most popular topics for potential posts, with 93.4 and 92.0% of patients endorsing interest respectively. The least popular topic was "Newborn photos and birth announcements," with only 47.4% endorsing interest. A little over half of respondents (56.3%) would feel comfortable with the clinic posting a picture of their infant. The vast majority of patients (96.2%) feel comfortable communicating electronically with their infertility clinic. CONCLUSION: Patients are interested in the use of social media as a forum for patient education and support in the infertility clinic. Patient preferences regarding post topics should be carefully considered.

Analysis of barriers to and patients' preferences for CT colonography for colorectal cancer screening in a nonadherent urban population.

OBJECTIVE: The aim of this study was to evaluate patients' barriers against colorectal cancer screening tests and to assess patients' preferences and cost influences for CT colonography (CTC) in a nonadherent urban subpopulation. SUBJECTS AND METHODS: Patients who had been offered colorectal cancer screening but were nonadherent were asked to participate in this questionnaire study. Patients' demographic information was obtained, and patients' reasons for not being screened were explored. Subjects were given an information sheet that described a CTC procedure and then were asked about their willingness to undergo CTC and about other relevant factors, such as fees. RESULTS: One hundred seventy-five patients were invited to participate; 53 declined and 54 did not respond, which left 68 subjects to be included in the analysis. After being informed about CTC screening, most (83%) subjects stated that they would be willing to undergo a CTC study. However, 70% stated that they would not be willing to pay out-of-pocket fees if insurance did not cover the study, and even among the 30% who were willing to pay the fees, the average amount they were willing to pay (mean, $244; median, $150) was well below currently charged rates. CONCLUSION: Our study suggests that most nonadherent patients would be willing to undergo CTC as long as out-of-pocket fees are reasonable.

Patient preferences for the chemoprevention of colorectal cancer.

Although evidence suggests that aspirin and celecoxib may reduce the risk of colorectal cancer (CRC), these drugs can also cause harmful side effects. The aim of this study was to characterize patient preferences for celecoxib and aspirin. Participants completed a computer-based patient decision-making questionnaire that included an educational component outlining the benefits and harms of celecoxib and aspirin. Under the base conditions 7.4% would take celecoxib and 43.6% would take aspirin; males were more willing than females to take aspirin. Patients identified the increased risk of myocardial infarction and gastrointestinal events as the primary reasons for their unwillingness to take celecoxib and aspirin, respectively. A majority of subjects would not take either drug, after considering their benefits and harms, although participants were almost six times more likely to take aspirin than celecoxib. These data serve to inform physicians and researchers regarding the variability and factors that affect patient preferences for CRC chemoprevention.

Factors associated with early in vitro fertilization treatment discontinuation.

OBJECTIVE: To investigate factors associated with early IVF treatment discontinuation. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Six hundred sixty-nine first-attempt IVF patients who did not have a live birth. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Treatment discontinuation and time to return for a second IVF cycle. RESULT(S): Women without IVF insurance coverage were more likely to discontinue treatment than women with insurance coverage (adjusted odds ratio [aOR] = 3.12; 95% confidence interval [CI], 2.22-4.40). African-American women were more likely to discontinue treatment (aOR = 2.95; 95% CI, 1.54-5.66) and returned for treatment more slowly (adjusted hazard ratio [aHR] = 0.44; 95% CI, 0.28-0.71) than non-Hispanic white women, regardless of IVF insurance coverage or income. Women with a poor prognosis were more likely to discontinue treatment than women with a good prognosis. Older women with IVF insurance coverage or a good prognosis had a shorter time to return for a second IVF cycle than older women without IVF insurance coverage or with a poor prognosis. Estimated income, distance to clinic, fertility diagnosis, number of oocytes retrieved, and history of previous live birth were not associated with treatment discontinuation or time to return for a second IVF cycle after adjustment for covariates. CONCLUSION(S): IVF insurance coverage, race, age, and future treatment prognosis are associated with IVF treatment discontinuation and time to return.

Patient preferences for the chemoprevention of esophageal adenocarcinoma in Barrett's esophagus.

OBJECTIVES: Although evidence suggests that aspirin and celecoxib may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE), these drugs can also cause harmful side effects. Our aim was to determine and characterize preferences for these two drugs in patients with BE. METHODS: Preferences data were collected from recruited BE patients using a customized questionnaire, which incorporated standard risk communication techniques. Summary profiles outlined the benefits and harms of celecoxib and aspirin presented anonymously. Both drugs were portrayed as reducing the risk of EAC and increasing the risk of GI events. However, celecoxib increased the risk of myocardial infarction (MI) while aspirin reduced the risk. Factors influencing patient acceptance of each drug were analyzed. RESULTS: One hundred of 109 (92%) subjects completed the study. Under base case conditions, 15% stated that they would take celecoxib and 76% aspirin (P < 0.0001). Patients identified the greater risk of MI as the primary reason for their unwillingness to take celecoxib and the lower risk of EAC for aspirin. Even in scenarios in which the benefits of celecoxib were improved and the harms reduced, a majority continued to find it unacceptable. CONCLUSIONS: A majority of those surveyed stated that they would take aspirin but would not take celecoxib. Most patients are interested in EAC chemoprevention, but the amount of protection and the side effect profile of a drug determine its acceptability. These data can inform physicians regarding the tradeoffs patients are willing to consider for chemoprevention.

Ultrasound-guided follicle aspiration at time of laparotomy in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: To demonstrate a unique case of direct ultrasound-guided follicle aspiration at time of a laparotomy in a patient with Mayer-Rokitansky-Küster-Hauser Syndrome. DESIGN: Video presentation. SETTING: Academic fertility center PATIENT(S): A 32-year-old gravida 0 with Mayer-Rokitansky-Küster-Hauser Syndrome and bilateral ovarian masses presented as a fertility preservation consult from gynecologic oncology due to the possibility of bilateral oophorectomy. Due to the appearance and size of the left ovary oncology planned to perform an exploratory laparotomy and left oophorectomy, with possible right oophorectomy. The patient and her partner desired embryo cryopreservation with plans for future use in a gestational carrier. She had previously undergone vaginal dilator therapy, however her ovaries were inaccessible transvaginally due to their cephalad location and small caliber of the vaginal pouch. The plan was made to proceed with controlled ovarian stimulation and concurrent ultrasound-guided follicle aspiration of the right ovary at the time of laparotomy following left oophorectomy. INTERVENTION(S): Ultrasound-guided follicle aspiration in vivo at time of laparotomy. MAIN OUTCOME MEASURE(S): Successful controlled ovarian stimulation, oocyte retrieval and embryo cryopreservation. RESULT(S): The patient underwent a long agonist protocol and received a total of 2,525 units of gonadotropin with a peak estradiol of 3,264 pg/ml. She required a total of 9 days of stimulation. The normal right ovary responded as expected, and the left ovary remained unchanged. Following laparotomy and left oophorectomy, direct application of the transvaginal ultrasound probe was used to aspirate all visible follicles on the right side in vivo. Twenty-four oocytes were retrieved, 15 were mature and 5 blastocysts were cryopreserved. Final pathology of left ovary returned as serous cystadenoma. The right ovary was examined by gynecologic oncology prior to and following retrieval and was thought to be normal and remained in situ. CONCLUSION(S): Although the approach described here is not feasible in most cases, this video demonstrates a unique and successful fertility preservation technique by direct ultrasound-guided follicle aspiration in vivo at the time of laparotomy in a Mayer-Rokitansky-Küster-Hauser Syndrome patient and to our knowledge, is the first description of its kind. This retrieval would have otherwise been limited by lack of access transvaginally and limited visualization transabdominally. This combined approach should be considered in future patients with müllerian anomalies and similar complicating factors necessitating laparotomy.

Obesity and female infertility: potential mediators of obesity's impact.

The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization. Obesity appears to affect the oocyte and the preimplantation embryo, with disrupted meiotic spindle formation and mitochondrial dynamics. Excess free fatty acids may have a toxic effect in reproductive tissues, leading to cellular damage and a chronic low-grade inflammatory state. Altered levels of adipokines, such as leptin, in the obese state can affect steroidogenesis and directly affect the developing embryo. The endometrium is also susceptible, with evidence of impaired stromal decidualization in obese women. This may explain subfecundity due to impaired receptivity, and may lead to placental abnormalities as manifested by higher rates of miscarriage, stillbirth, and preeclampsia in the obese population. Many interventions have been explored to mitigate the effect of obesity on infertility, including weight loss, physical activity, dietary factors, and bariatric surgery. These data are largely mixed, with few high quality studies to guide us. As we improve our understanding of the pathophysiology of obesity in human reproduction we hope to identify novel treatment strategies.

A Focused Look at Obesity and the Preimplantation Trophoblast.

Obesity is associated with a myriad of adverse reproductive outcomes including miscarriage, fetal growth abnormalities, and preeclampsia. While the mechanisms involved are likely multifactorial, the potential impact of obesity on the preimplantation embryonic trophoblast cannot be overlooked-particularly given the role the trophoblast plays in endometrial invasion and implantation. Appropriate trophoblast function is critical in establishing a normal pregnancy. Insufficient or impaired trophoblast invasion is associated with early miscarriage, fetal growth abnormalities, and preeclampsia. Thus, any negative impact obesity may impose on the trophoblast may represent a root cause for several adverse reproductive outcomes seen more commonly among obese women. While little is known about obesity's specific impact on the human trophoblast, in vitro studies and animal models provide insight. In this article, we review what is known on this topic and provide a basis for future work, investigating therapeutic targets for improved reproductive outcomes in the setting of maternal obesity.

Best practices for controlled ovarian stimulation in in vitro fertilization.

As applications for IVF have expanded over the years, so too have approaches to controlled ovarian stimulation (COS) for IVF. With this expansion and improved knowledge of basic reproductive biology, there is increasing interest in how COS practice influences IVF outcomes, and whether or not specific treatment scenarios call for personalized approaches to COS. For the majority of women undergoing COS and their treating physicians, the goal is to achieve a healthy live birth through IVF in a fresh cycle. Opinions on how COS strategy best leads to this common goal varies among centers as many clinicians base COS strategy not on evidence obtained through prospective randomized trials, but rather through observational studies and experience. Overall, when it comes to COS most clinicians recognize the approach should not be "one size fits all," but rather a patient-centered approach that takes the existing evidence into consideration. We outline the existing evidence for best practices in COS for IVF, highlighting how these practices may be incorporated into a patient-centered approach.