A Fluid-Management Drape for Hysteroscopy: Innovation for Improved Patient Safety and Surgical Care.

BACKGROUND: Hysteroscopy requires accurate collection of unabsorbed distension media to measure patient fluid absorption. We assessed the effectiveness and usability of a novel total capture drape compared with a standard drape during hysteroscopy. METHOD: Simulation trials were followed by an early-phase study to compare fluid-capture efficiency and measures of drape usability during hysteroscopy randomizing the total capture drape compared with a standard drape. EXPERIENCE: Simulation trials indicated complete collection of unabsorbed fluid with the total capture drape and progressive loss of unabsorbed fluid with the standard drape. An early-phase study with 68 women found no statistical difference between groups for the hysteroscopic fluid deficit, but saw fewer cases with lost fluid in the total capture drape compared with the standard drape. Direct observation and focus group data indicated a trend for better capture of unabsorbed fluid with the total capture drape, along with increased usability once surgeons became familiar with correct placement. CONCLUSION: Simulation and early-phase study results are favorable for the total capture drape, demonstrating comparable fluid collection with the standard drape. With repeated use and in-service training, surgeons expressed greater confidence in the accuracy of the hysteroscopic fluid deficit with the total capture drape compared with the standard drape. Design modifications should improve overall usability and fluid-capture efficiency.

Androgenicity and fertility treatment in women with unexplained infertility.

OBJECTIVE: To determine whether biochemical or clinical markers of androgenic activity predict live birth rate with ovarian stimulation in the unexplained infertility population. DESIGN: Secondary analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): Nine hundred couples with unexplained infertility were included. Women were 18-40 years old with regular menses, a normal uterine cavity, at least one patent fallopian tube, and a male partner with ≥5 million motile sperm. Women were randomized to receive gonadotropin, clomiphene, or letrozole with IUI for four or fewer four treatment cycles. Women were evaluated for biochemical (total testosterone, DHEAS, and free androgen index) and clinical markers of androgenic activity (sebum, acne, and hirsutism). Multivariable logistic regression models adjusting for treatment group, maternal age, and body mass index were performed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Secondary outcomes included conception, clinical pregnancy, and pregnancy loss. RESULT(S): When comparing 900 women in the AMIGOS trial based on quartiles of serum TT, women were of younger age, higher body mass index, and higher waist circumference with increasing TT. Increasing quartiles of TT also showed increasing DHEAS and free androgen index values. Serum androgens were not associated with outcomes of live birth, conception, clinical pregnancy, or pregnancy loss. Clinical androgen markers were not associated with pregnancy outcomes. CONCLUSION(S): In a randomized cohort of women with unexplained infertility, biochemical and clinical measures of androgens did not predict live birth rate after ovarian stimulation treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.

Subclinical Hypothyroidism: Impact on Fertility, Obstetric and Neonatal Outcomes.

The incidence of subclinical hypothyroidism (SCH) in pregnancy was classically thought to be low; however, with new definition of normal TSH range in pregnancy, there has been an increase in the percentage of women who meet classification for SCH. The diagnosis of SCH is important not only for monitoring for maternal conversion to overt hypothyroidism, but also for identifying obstetric and neonatal outcomes related to SCH. Although there have been proven associations between maternal overt hypothyroidism and adverse obstetric and neonatal outcomes, there has been conflicting data on the correlation between SCH and these outcomes. Recent data from a meta-analysis found an increased risk of pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death for women with SCH compared to euthyroidism in pregnancy. Research studies have not demonstrated a distinct benefit from treatment of SCH, and the professional societies are divided on their recommendations for treating SCH. Additionally, universal screening of SCH is controversial at present.

Recruitment strategies in two reproductive medicine network infertility trials.

BACKGROUND: Recruitment of individuals into clinical trials is a critical step in completing studies. Reports examining the effectiveness of different recruitment strategies, and specifically in infertile couples, are limited. METHODS: We investigated recruitment methods used in two NIH sponsored trials, Pregnancy in Polycystic Ovary Syndrome (PPCOS II) and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), and examined which strategies yielded the greatest number of participants completing the trials. RESULTS: 3683 couples were eligible for screening. 1650 participants were randomized and 1339 completed the trials. 750 women were randomized in PPCOS II; 212 of the participants who completed the trial were referred by physicians. Participants recruited from radio ads (84/750) and the internet (81/750) resulted in similar rates of trial completion in PPCOS II. 900 participants were randomized in AMIGOS. 440 participants who completed the trial were referred to the study by physicians. The next most successful method in AMIGOS was the use of the internet, achieving 78 completed participants. Radio ads proved the most successful strategy in both trials for participants who earned <$50,000 annually. Radio ads were most successful in enrolling white patients in PPCOS II and black patients in AMIGOS. Seven ancillary Clinical Research Scientist Training (CREST) sites enrolled 324 of the participants who completed the trials. CONCLUSIONS: Physician referral was the most successful recruitment strategy. Radio ads and the internet were the next most successful strategies, particularly for women of limited income. Ancillary clinical sites were important for overall recruitment.

On-label and off-label drug use in the treatment of female infertility.

Female infertility affects millions of couples worldwide and is estimated to account for one-third of all cases of infertility. The purpose of this article is to review the uses of both off-label treatments and those approved by the US Food and Drug Administration for female infertility, by examining the mechanism of action, the side-effect profile, fetal anomaly risks, and contraindications for the various drugs.

Endocrine and reproductive effects of polycystic ovarian syndrome.

Management strategies for overweight and obese women with polycystic ovarian syndrome (PCOS) who desire fertility should include weight loss. Even a small reduction in body weight can improve ovulatory function and pregnancy rate and reduce adverse obstetric outcomes. New data suggest that letrozole should be considered as the new first-line medical treatment of anovulatory infertility in PCOS over clomiphene citrate. Second-line treatments for anovulatory infertility include in vitro fertilization, gonadotropins, or ovarian drilling.

Sexual absorption of vaginal progesterone: a randomized control trial.

Objective. To determine if sexual intercourse reduces absorption of vaginal progesterone gel in women and to determine if progesterone is absorbed by the male during intercourse. Study Design. Prospective, randomized, cross over, controlled study of 20 reproductive-aged women and their male sexual partners randomized to receive vaginal progesterone gel (Crinone 8% gel, Actavis Inc., USA) or placebo cream. Serum progesterone for both male and female partners were measured 10 hours after intercourse. One week later, subjects were crossed over to receive the opposite formulation. In the third week, women used progesterone gel at night and abstained from intercourse. Results. Serum progesterone was significantly reduced with vaginal progesterone gel + intercourse compared with vaginal progesterone gel + abstinence (P = 0.0075). Men absorbed significant progesterone during intercourse with a female partner using vaginal progesterone gel compared to placebo (P = 0.0008). Conclusion(s). Vaginal progesterone gel is reduced in women after intercourse which may decrease drug efficacy during luteal phase support. Because men absorb low levels of progesterone during intercourse, exposure could cause adverse effects such as decreased libido. This study is registered under Clinical Trial number NCT01959464.

Influence of ejaculatory abstinence on seminal total antioxidant capacity and sperm membrane lipid peroxidation.

OBJECTIVE: To determine whether the period of ejaculatory abstinence (EA) influences the total antioxidant capacity (TAC) of semen or lipid peroxidation (LPO) of sperm membranes. DESIGN: A prospective experimental trial. SETTING: Academic medical center for reproductive endocrinology and infertility. PATIENT(S): Forty men from infertile couples planning intrauterine insemination. INTERVENTION(S): Men provided semen specimens after EA periods of 1 and 4 days. MAIN OUTCOME MEASURE(S): Semen analysis, peroxidase staining, and assays for seminal TAC and sperm membrane LPO, with measures compared between days 1 and 4 within individuals (internal control) using paired t tests. RESULT(S): The shorter period of EA (1 day vs. 4 days) resulted in statistically significant decreases in semen volume (-24%), sperm density (-28%), and total sperm count (-3.2%). There was a statistically significant increase in TAC with the shorter period of EA (1 day) compared with 4 days of EA. No difference was detected in sperm membrane LPO comparing 1 day of EA and 4 days of EA. CONCLUSION(S): Higher seminal TAC obtained after a shorter period of EA could diminish oxidative stress-induced sperm damage by a mechanism independent of LPO. Shorter periods of EA may thus improve sperm quality by protecting from reactive oxygen species damage, even though lower numbers of motile sperm are produced after a shorter period of EA. This would be consistent with prior research indicating improved results after intrauterine insemination under these circumstances.

Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome.

OBJECTIVE: To determine how often women with Ehlers-Danlos syndrome experience obstetric and gynecologic issues both compared with the general population and within the three most common subtypes of Ehlers-Danlos syndrome. METHODS: An anonymous, prospective, online questionnaire in English was posted to the Ehlers-Danlos National Foundation web site (http://ednf.org). RESULTS: Of the 1,769 of those who completed the survey, 1,225 reported a typed diagnosis of Ehlers-Danlos syndrome. Further stratification to the three most common types and reproductive-aged women (n=775) allowed conclusions to be made about differences in rates of obstetric complications and gynecologic dysfunction compared with the general population and between types of Ehlers-Danlos syndrome. Rates of obstetric outcomes for women who reported at least one pregnancy included term pregnancy in 69.7%, preterm birth in 25.2%, spontaneous abortion in 57.2%, and ectopic pregnancy in 5.1%. Infertility was reported by 44.1% of survey respondents. Normal menstrual cycles were reported by only 32.8% with intermenstrual bleeding occurring in 18.6%. Heavy menstrual bleeding was reported by 32.9% survey participants. Gynecologic pain reported included dysmenorrhea by 92.5% and dyspareunia by 77.0%. CONCLUSION: There is a much greater prevalence of obstetric and gynecologic issues reported by women with Ehlers-Danlos syndrome than in the general population. Additionally, rates differed significantly among the three most common types of Ehlers-Danlos syndrome with vascular type having the highest rates of adverse pregnancy outcomes and menstrual abnormalities. Physician providers should be aware of these challenges and should counsel patients with Ehlers-Danlos syndrome about relevant options and risks.

Association of blood type and patient characteristics with ovarian reserve.

OBJECTIVE: To assess whether blood type was associated with diminished ovarian reserve (DOR) (day-3 follicle-stimulating hormone level >10 IU/L), controlling for history of tobacco smoking, body mass index (BMI), history of endometriosis, ovarian surgery, previous pregnancy, and maternal age. DESIGN: Cross-sectional study. SETTING: Academic medical center, Division of Reproductive Endocrinology and Infertility. PATIENT(S): Women undergoing in vitro fertilization (IVF) from 2006-2011 (n = 305). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Presence of DOR in relation to a patient's blood type. RESULT(S): Other investigators have reported an increased risk for DOR in patients with blood type O and a protective effect on ovarian reserve for blood type A. We observed no association between a woman's blood type and DOR. We found an increased risk for DOR in patients aged 35 and older. Obesity (BMI ≥ 30 vs. BMI <25) was associated with lower odds of DOR. CONCLUSION(S): In comparison with blood type A, blood type O is not associated with an increase in DOR. We found no clinical implications for using blood type as a risk factor for DOR.

The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval.

OBJECTIVE: To study the effect of ketorolac, a potent anti-inflammatory medication, on in vitro fertilization (IVF) pregnancy outcomes when used at the time of oocyte retrieval. DESIGN: Retrospective review of 454 patients from 2003-2009. SETTING: Tertiary hospital-affiliated fertility center. PATIENT(S): Consecutive subfertile women undergoing their first IVF cycle. INTERVENTION(S): Ketorolac administration immediately after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy, implantation, live-birth, and miscarriage rates, and postsurgical visual analog pain score. RESULT(S): Of the 454 patients undergoing their first IVF cycle for all indications, 103 received intravenous ketorolac immediately after oocyte retrieval, based on anesthesiologist preference. Patient and procedural characteristics were similar between both groups. The use of ketorolac had no effect on the rates of implantation, miscarriage, pregnancy, live birth, or multiple pregnancy. The patients receiving ketorolac experienced statistically significantly less pain. CONCLUSION(S): This study suggests ketorolac has no apparent detrimental effect on IVF pregnancy outcomes when administered immediately after oocyte retrieval. Ketorolac appears to be a safe and effective analgesic to use at the time of oocyte retrieval.

Reproductive impact of polycystic ovary syndrome.

PURPOSE OF REVIEW: The purpose of this review is to highlight the impact of polycystic ovary syndrome (PCOS) on menstrual function, fertility and reproductive outcomes. Women with PCOS often present with anovulation, menstrual disturbances and hyperandrogenism. Management options for the reproductive disorders of PCOS will be discussed. RECENT FINDINGS: The role of metformin in treating PCOS is narrowing. New data show improved live birth rates by skipping a progestin withdrawal bleed and proceeding directly with a dose escalation of clomiphene for ovulation induction. The Pregnancy in PCOS trial II will determine the safety and efficacy of clomiphene citrate compared to letrozole, in achieving live birth in infertile women with PCOS. SUMMARY: Initial treatment for reproductive disorders in overweight and obese women with PCOS is weight loss. This helps menstrual disturbances, shortens the time to conception and reduces adverse obstetric risks. Clomiphene citrate is considered the first-line therapy for ovulatory infertility. Clomiphene citrate-resistant women may be offered aromatase inhibitors or laparoscopic ovarian surgery. Metformin does not improve live birth rate or reduce miscarriage rate and is no longer considered an option for ovulation induction. Women with PCOS need to be counseled about risks of multiple gestations with gonadotropin therapy.

Cancer, fertility preservation, and future pregnancy: a comprehensive review.

Given the increases in 5-year cancer survival and recent advances in fertility preserving technologies, an increasing number of women with cancer are presenting for discussion of fertility preserving options. This review will summarize the risk of infertility secondary to cancer treatment, available treatment options for fertility preservation, and techniques to reduce future risks for patients. Concerns that will be addressed include the risk of the medications and procedures, the potential delay in cancer treatment, likelihood of pregnancy complications, as well as the impact of future pregnancy on the recurrence risk of cancer. Recent advances in oocyte cryopreservation and ovarian stimulation protocols will be discussed. Healthcare providers need to be informed of available treatment options including the risks, advantages, and disadvantages of fertility preserving options to properly counsel patients.

Effects of variations in serum estradiol concentrations on secretory endometrial development and function in experimentally induced cycles in normal women.

Eighteen normal women underwent pituitary down-regulation with leuprolide, followed by a 10-day treatment with 0.2 mg/d transdermal estradiol (E(2)) with subsequent allocation to one of two 10-day estradiol regimens plus 40 mg daily intramuscular P: supraphysiologic (0.2 mg/d transdermal E(2) mg/d vaginal micronized E(2)) or subphysiologic (no exogenous E(2) treatment). Average E(2) and P in the supraphysiologic, physiologic, and subphysiologic groups were 1,175.9 pg/mL and 17.5 ng/mL, 136.9 pg/mL and 21.2 pg/mL, and 23.8 ng/mL and 22.0 ng/mL, respectively, and there were no differences between groups in endometrial histology or expression of biomarkers of receptivity.

Novel clomiphene "stair-step" protocol reduces time to ovulation in women with polycystic ovarian syndrome.

OBJECTIVE: The objective of the study was to determine the efficacy of a novel "stair-step" clomiphene protocol in women with polycystic ovarian syndrome (PCOS) who do not respond to 50 mg clomiphene. STUDY DESIGN: This was a retrospective analysis at an academic fertility center. The stair-step protocol is performed as follows: 50 mg clomiphene for 5 days, ultrasonography on days 11-14. If unresponsive, immediately begin 100 mg clomiphene for 5 days and repeat ultrasound in 1 week. If still unresponsive, begin 150 mg clomiphene for 5 days and repeat the ultrasound in 1 week. Stair-step cycles were compared with published historical clomiphene outcomes for women who were nonresponsive. RESULTS: The time to ovulation was 32-53 days less with the stair-step protocol compared with a traditional regimen. The dose-dependent ovulation rate was 64% at 100 mg with the stair-step protocol compared with 22% with a traditional regimen. CONCLUSION: It is not necessary to induce menses before increasing clomiphene doses in nonresponsive PCOS patients.

Endometrial development and function in experimentally induced luteal phase deficiency.

CONTEXT: It is generally assumed that delayed endometrial development observed in luteal phase deficiency (LPD) is the result of abnormally low progesterone (P) levels. This hypothesis has never been tested by direct experiment. OBJECTIVE: Our objective was to evaluate the effects of P concentrations on human endometrium. DESIGN AND SETTING: A randomized trial was conducted at an academic medical center. SUBJECTS: Twenty-nine healthy, ovulatory 18- to 35-yr-old women participated. INTERVENTION: Endometrial samples were obtained from women in natural cycles and two groups of experimentally modeled cycles. Women undergoing modeled cycles were treated with GnRH agonist and a fixed physiological dose of transdermal estradiol, followed by randomization to 10 or 40 mg daily im P administration to achieve either normal circulating luteal P or 4-fold lower P concentrations, the latter representing an experimental model of LPD. MAIN OUTCOME MEASURES: Tissue specimens, obtained after 10 days of P exposure, were analyzed by histological dating, immunohistochemistry, immunoblot, and real-time quantitative RT-PCR (qRT-PCR). RESULTS: Histological dating of endometrium, immunohistochemistry for endometrial integrins, and qRT-PCR analysis for nine putative functional markers showed no differences between the three groups. Preliminary data from Western analysis suggest that some proteins may be affected by low serum P concentrations. CONCLUSIONS: Histological endometrial dating does not reflect circulating P concentrations and cannot serve as a reliable bioassay of the quality of luteal function. Assessment of selected functional markers by either immunohistochemistry or qRT-PCR is similarly insensitive to decreased circulating P. Preliminary evidence suggests that abnormally low luteal phase serum P concentrations may have important functional consequences not otherwise detected.

The impact of uterine artery embolization on fertility and pregnancy outcome.

PURPOSE OF REVIEW: Uterine artery embolization for management of symptomatic fibroids is an effective and increasingly popular treatment option. There are several studies evaluating the effects of uterine artery embolization on later pregnancies; however, the effects on fertility are still largely uncertain. This paper reviews the current literature on the effects of this technique on fertility and pregnancy outcome. RECENT FINDINGS: Two recent studies have reported pregnancy rates following uterine artery embolization in women seeking pregnancy. A small, third study reported preliminary results in a randomized controlled trial comparing uterine artery embolization with myomectomy in women wishing to preserve fertility. SUMMARY: The body of medical literature supports use of uterine artery embolization as an effective treatment for symptoms of vaginal bleeding and pelvic pressure from uterine fibroids. Patient selection is critical in determining the appropriateness of this treatment option. Myomectomy remains the standard of care for women with symptomatic fibroids seeking fertility preservation.

Assisted reproductive technology (ART) in the upstate: reducing the risks of multiple births.

Multiple pregnancies from ART procedures are all too common. Efforts to reduce high-order multiple pregnancies will require both social and medical reforms. In lieu of a legislative agenda to reduce multiple pregnancies in the United States, efforts must come from the personnel within the individual ART clinics. The approach to the problem includes accepting a lower pregnancy rate than otherwise might be obtainable, if the observed rate of high-order multiple pregnancies is above a certain threshold. Expanding the opportunities for ART reimbursement will ultimately address this problem in the United States, but until then, it is a problem that will not go away without commitment and resolve.

Temporal and morphologic characteristics of pinopod expression across the secretory phase of the endometrial cycle in normally cycling women with proven fertility.

OBJECTIVE: To assess the temporal and morphologic characteristics of pinopod expression on the surface of endometrium across the secretory phase, in LH-timed endometrial samples in normal, healthy women. DESIGN: Prospective, randomized study. SETTING: Academic teaching hospital. PATIENT(S): Sixty-eight healthy volunteers with proven fertility. INTERVENTION(S): Urinary LH-timed endometrial and blood sampling was performed on each subject on a randomly selected day of the secretory phase. MAIN OUTCOME MEASURE(S): Histologic dating, assessment of pinopods using scanning electron microscopy, and comparison with serum P levels. RESULT(S): Eighty-six endometrial tissue samples obtained from 68 subjects were evaluated under scanning electron microscopy. Pinopods were first observed on luteal day 5, corresponding with the onset of the midluteal phase increase in serum P levels. Pinopods persisted for the entire duration of the secretory phase, but their morphology changed as the cycle advanced. CONCLUSION(S): The present findings demonstrate that pinopods are a characteristic feature of the mid to late secretory phase endometrial epithelium, exhibit cycle-dependent changes in morphology, and are most prominent during the putative implantation interval.