Randal D. Robinson

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.).

DEVELOPMENT OF BRIEF STRESS MANAGEMENT SUPPORT GROUPS FOR COUPLES UNDERGOING IN VITRO FERTILIZATION TREATMENT

OBJECTIVE To develop and assess the efficacy of couples stress management groups offered concurrently with IVF treatment. DESIGN Couples in IVF treatment were given the option of participating in a biweekly stress management group. SETTING The IVF treatment clinic at Wilford Hall Medical Center, San Antonio, Texas. PATIENT(S) One or both members of 17 couples participated in the program in one of four group cycles. INTERVENTION(S) A cognitive behavioral treatment model was used to help couples process their feelings and cognitions about the impact of infertility on their life and explore their expectations about their future options for becoming parents. MAIN OUTCOME MEASURE(S) Couples were asked to anonymously evaluate the efficacy of the group after they had completed their IVF cycle. RESULT(S) Participants reported that the group helped them deal with the stress of infertility and that they valued the social bonds they formed with other group members. CONCLUSION(S) These data suggest that brief focused group therapy, offered while couples are undergoing IVF, is an effective way to help people deal with the stress of infertility treatment.

Do U.S. Medical Licensure Examination Step 1 Scores Correlate with Council on Resident Education in Obstetrics and Gynecology In-Training Examination Scores and American Board of Obstetrics and Gynecology Written Examination Performance?

OBJECTIVE The purpose of this study was to assess the possible association between scores of >200 on U.S. Medical Licensure Examination (USMLE) step 1 and the Council on Resident Education in Obstetrics and Gynecology (CREOG) in-training examinations and the pass rate on the American Board of Obstetrics and Gynecology (ABOG) written examination. METHODS The USMLE step 1 and postgraduate year 1 to 4 CREOG in-training examination scores for the graduating chief residents in eight accredited obstetrics and gynecology residency programs were obtained. Performance on USMLE step 1 was correlated with ABOG examination performance and CREOG in-training examination scores. The correlations between USMLE step 1 and CREOG in-training examination scores and ABOG examination performance were analyzed by using the Spearman correlation coefficient. RESULTS USMLE step 1 scores were significantly correlated with CREOG in-training examination scores (p < 0.000). None of the residents who scored >200 on USMLE step 1 and a mean of >200 on the CREOG in-training examinations failed the ABOG written examination. CONCLUSION Program directors have used USMLE step 1 to identify trainees who are likely to perform well on the CREOG in-training examination. The CREOG in-training examination has been used to identify residents who are likely to pass the ABOG written examination. The results of this study document the strength of these associations.

Will decreasing assisted reproduction technology costs improve utilization and outcomes among minority women

OBJECTIVE To evaluate assisted reproduction technology (ART) usage and outcomes in minority women seeking care at enhanced access, military ART programs. DESIGN Retrospective cohort. SETTING Federal ART programs. PATIENT(S) Two thousand fifty women undergoing first cycle, fresh, nondonor ART from 2000 to 2005. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Rate of ART use, clinical pregnancy rate, live birth rate. RESULT(S) African American women had an almost fourfold increased use of ART and Hispanic women had decreased use. Clinical pregnancy rates were significantly lower for African American women compared with white women (46.1% vs. 52.6%, relative risk [RR] 0.88; 95% confidence interval [CI], 0.78-0.99) as were live birth rates (33.7%. vs. 45.7%, RR 0.74; 95% CI, 0.63-0.91). CONCLUSION(S) Economics appear to influence ART use by African American women but not Hispanic women. Despite increased use by African American women, outcomes in this group were worse when compared with Caucasian women. Improving access through decreased cost may increase use by some but not all minority groups. Improved access may not translate into improved outcomes in some ethnic groups.

Efficacy of brief couples support groups developed to manage the stress of in vitro fertilization treatment

OBJECTIVE To assess the efficacy of brief couples support groups offered concurrently with in vitro fertilization (IVF) treatment. PATIENTS AND METHODS Couples in IVF treatment were given the option of participating in a biweekly support group at the IVF clinic at Wilford Hall Medical Center, San Antonio, Tex. At least 1 member of 26 couples participated in the brief couples support groups, and at least 1 member of 19 other couples completed the questionnaires but did not attend the support group sessions and so comprised the control group. Facilitators used cognitive behavioral techniques to help participants process their feelings and cognitions about their infertility. Emotional and cognitive factors were assessed both before and after group attendance by using the Beck Depression Inventory; the Beck Anxiety Inventory; the Life Orientation Test, which assesses optimism and pessimism; the Survey of Personal Views, which measures irrational beliefs; and the Social Provisions Scale, which measures social support. RESULTS Women who attended group sessions were significantly less anxious after the IVF treatment than they were before the cycle (P < .001). Men who attended the group sessions were more optimistic than nongroup men or the women at the completion of the IVF cycle (P < .001) but endorsed greater numbers of irrational beliefs (P < .001). CONCLUSIONS Despite the fact that the service was relatively inexpensive compared with IVF in the civilian community, the complexity of IVF treatment and the logistic and psychological stress experienced by couples made it hard to form and maintain such groups. Nevertheless, both men and women derived psychological benefit from the group: women reported less anxiety and men greater optimism on completion of the group sessions.

Menopause and depression: A review of psychologic function and sex steroid neurobiology during the menopause

The purpose of this review is threefold. The first objective is to assess from current literature the extent to which depressive symptoms may be associated with peri- and postmenopausal states. Although there have been many studies published addressing this topic, there remains much controversy as to whether there is a true positive correlation of increased depressive symptomatology with the peri- and postmenopausal periods. Second, sex steroid neurobiology will be reviewed. In recent years, improved technology has allowed for much more detail in investigations of the central mechanisms of action of the sex hormones. Ultimately, estrogen appears to play an excitatory role in the central nervous system, whereas progesterone has been shown to be inhibitory. The third objective is to determine whether sex steroids have been shown to clinically affect mood and psychologic function, and if so, how such information might relate to regimens for peri- and postmenopausal hormone replacement. Currently, only large, pharmacologic doses of estrogen have been shown to improve mood in clinically depressed patients. Estrogen has been shown to potentiate the effects of some antidepressants; therefore menopausal women with major depressive disorders may respond to lower doses of antidepressant medications when estrogen replacement is added to the treatment regimen.The psychological and physiological manifestations in depressive illnesses of the post-menopausal age period are of great complexity and not clearly understood. In view of the obscurity of the etiological factors it is important to isolate and study the effect of one such possible factor at a time.1Many symptoms and signs of various mood disturbances have been attributed to estrogen deficiency during the climacteric, yet it has been argued that there are no psychological symptoms specific to the menopause. The literature concerning psychological symptoms accompanying menopause is confusing.2Taken from studies published more than 50 years apart, these quotes describe the long-standing difficulty investigators have faced in evaluating psychologic function during the menopause. From the 1930s to the present, ongoing debate has surrounded issues of depression associated with the peri- and postmenopausal periods: whether there is an association at all and if so, what the cause might be and how might it be treated. Investigators continue to add new information to this debate, driven by the common understanding that issues relating to menopause and the postmenopausal period have become increasingly important. Not only are greater numbers of women approaching menopause, but these women are now expected to live greater than one third of their lives after menopause.3 The purpose of this review is first to assess from the literature the extent to which depressive symptoms may be associated with peri- and postmenopausal states. Second, in an attempt to explain or define causes of proposed changes in psychologic function during menopause, sex steroid neurobiology will be reviewed. The last objective is to determine from the literature whether sex steroids as used in hormone replacement therapy have been shown to clinically affect mood and psychological function and if so, how such information might relate to regimens for peri- and postmenopausal hormone replacement.

Robotic surgery applications in the management of gynecologic malignancies.

This review evaluates the use of robotic‐assisted laparoscopic surgery in the treatment of gynecologic malignancies and objectively evaluates the use of these systems in performing radical hysterectomies and surgical staging of gynecologic malignancies. The review focuses on surgical length, blood loss, complications, recovery time, and adequacy of surgical staging of robotic‐assisted surgery compared to abdominal and non‐robotically assisted laparoscopic surgery for malignancies.

Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics

OBJECTIVE To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN Randomized, prospective clinical trial. SETTING Multicenter university-based clinical practices. PATIENT(S) A total of 900 couples with unexplained infertility. INTERVENTION(S) Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S) Demographic, laboratory, imaging, and survey characteristics. RESULT(S) Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S) The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER NCT 01044862.

Impact of day 3 or day 5 embryo transfer on pregnancy rates and multiple gestations

OBJECTIVE To test the hypothesis that day 5 ET (D5ET) is superior to day 3 ET (D3ET) in pregnancy outcome and that it also reduces multiple gestations. DESIGN Retrospective cohort study. SETTING Assisted reproductive technologies program at Wilford Hall Medical Center. PATIENT(S) Patients electing for either D3ET or D5ET. INTERVENTION(S) Participants meeting inclusion criteria for D5ET elected either D3ET or D5ET. MAIN OUTCOME MEASURE(S) Cycles were compared by day of transfer and further stratified by patient age (<35 years and 35-40 years). The number of oocytes retrieved, embryos on day 3, embryos transferred, pregnancy rate, implantation rate, and twin and high order multiples (>or=triplets) rates were compared. RESULT(S) Of the 274 patients who met our inclusion criteria, 153 underwent a D3ET and 121 underwent a D5ET. The D5ET group had a significantly lower mean age and number of embryos transferred and a higher implantation rate (56% vs. 42%) than the D3ET group. Patients who were 35-40 years old had a significantly higher live-birth rate (68% vs. 40%). Although not statistically significant, the D5ET groups had higher clinical pregnancy (73% vs. 65%) and twin pregnancy (33% vs. 25%) rates. CONCLUSION(S) Blastocyst transfer resulted in fewer embryos transferred, with a trend toward improved clinical pregnancy and higher twin pregnancy rates. Live-birth rates were improved in patients 35-40 years of age. Younger patients opting for D5ET should do so with a commitment toward single ET.

Fertility Preservation Counseling for Pediatric and Adolescent Cancer Patients

PURPOSE Fertility preservation for children and young adults with cancer is an important part of comprehensive patient care. In 2013, the American Society of Clinical Oncology (ASCO) released updated clinical practice guidelines addressing fertility preservation. This study aimed to evaluate if pediatric oncologists were performing fertility preservation counseling, if the new guidelines were being adopted, and how reproductive endocrinologists can educate this patient population and their providers. METHODS A cross-sectional study was performed from May 26, 2014, to August 26, 2014. An online survey addressing fertility preservation practice patterns was created and provided to the members of the Childrens Oncology Group (COG). RESULTS Thirty-five percent of the 234 respondents reported reading the new 2013 ASCO guidelines. Ninety-five percent of providers reported mentioning fertility preservation options prior to treatment, most commonly including referral to a reproductive endocrinologist (28%), and sperm banking (57%). The most commonly reported barrier to fertility preservation counseling was the cost of treatment. CONCLUSION Fertility preservation counseling is being performed by pediatric oncology providers. Familiarity of the ASCO guidelines is limited, revealing that the established methods for fertility preservation in women--embryo and oocyte cryopreservation--may be offered less than experimental methods in this younger patient population. Such differences in apparent practice patterns highlight the need for more education for providers.