A. Albert Yuzpe

Psychological assessment and follow-up after in vitro fertilization: assessing the impact of failure

The present study was conducted to assess the immediate psychological impact of failed in vitro fertilization (IVF). Emotional status and marital functioning were also examined pre-IVF, and both demographic information and psychological test scores were evaluated as predictors of reaction to treatment failure. After a failed first cycle, both males and females showed significant increases in anxiety and depressive symptoms. Although group means were not clinically elevated and most participants were coping adequately, the prevalence of both mild and moderate depression increased substantially, particularly among women. In addition, women without children were a subgroup particularly vulnerable to the stress of failure. Predisposition towards anxiety, pre-IVF depressive symptoms, and fertility history were the most important predictors of emotional response. Treatment implications of these findings were discussed.

A multicenter clinical investigation employing ethinyl estradiol combined with dl-norgestrel as a postcoital contraceptive agent*

Six hundred ninety-two women were enrolled in a multicenter clinical trial to evaluate a combination of ethinyl estradiol and dl-norgestrel as a postcoital contraceptive. When compared with various formulas predicting the probability of pregnancy in this group, the number of pregnancies observed appears to be reduced by approximately 84%. The combination of 200 micrograms of ethinyl estradiol and 2 mg of dl-norgestrel seems to be effective as a postcoital contraceptive with several advantages over estrogens alone.

Estimating the prevalence of infertility in Canada

BACKGROUND Over the past 10 years, there has been a significant increase in the use of assisted reproductive technologies in Canada, however, little is known about the overall prevalence of infertility in the population. The purpose of the present study was to estimate the prevalence of current infertility in Canada according to three definitions of the risk of conception. METHODS Data from the infertility component of the 2009–2010 Canadian Community Health Survey were analyzed for married and common-law couples with a female partner aged 18–44. The three definitions of the risk of conception were derived sequentially starting with birth control use in the previous 12 months, adding reported sexual intercourse in the previous 12 months, then pregnancy intent. Prevalence and odds ratios of current infertility were estimated by selected characteristics. RESULTS Estimates of the prevalence of current infertility ranged from 11.5% (95% CI 10.2, 12.9) to 15.7% (95% CI 14.2, 17.4). Each estimate represented an increase in current infertility prevalence in Canada when compared with previous national estimates. Couples with lower parity (0 or 1 child) had significantly higher odds of experiencing current infertility when the female partner was aged 35–44 years versus 18–34 years. Lower odds of experiencing current infertility were observed for multiparous couples regardless of age group of the female partner, when compared with nulliparous couples. CONCLUSIONS The present study suggests that the prevalence of current infertility has increased since the last time it was measured in Canada, and is associated with the age of the female partner and parity.

Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain

OBJECTIVES To determine the effectiveness of a 3-month course of nafarelin and, furthermore, to determine the long-term efficacy in patients treated for 3 and 6 months with nafarelin for symptoms associated with endometriosis. DESIGN Double-blind, prospective, multicenter, clinical trial. SETTING Fifteen reproductive endocrine clinics throughout the United States. PATIENTS One hundred seventy-nine women with pelvic pain and endometriosis. INTERVENTIONS Patients were assigned randomly to 3 months nafarelin followed by 3 months of placebo (n = 91) or to 6 months nafarelin (n = 88) in a prospective, randomized, double-blind multicenter trial. Patients were followed for 12 months after cessation of therapy. MAIN OUTCOME MEASURES Patient-reported pain scores and physician-reported physical exam findings. RESULTS Pain scores dropped significantly by the end of treatment in both groups. Symptoms recurred in both groups, and pain scores gradually increased during the follow-up period but always remained below baseline in both groups. No significant difference in efficacy was noted between the groups. A total of 26% of patients in each group underwent retreatment for recurrent symptoms. CONCLUSIONS A 3-month course of nafarelin provided effective symptom relief for endometriosis. One year follow-up demonstrated continued pain relief but with gradual return of symptoms.

Withholding gonadotropins (“coasting”) to minimize the risk of ovarian hyperstimulation during superovulation and in vitro fertilization–embryo transfer cycles

OBJECTIVE To evaluate superovulation (SOV) and IVF-ET cycles in which E2 levels were allowed to decrease to restrain rapid follicular growth and minimize the risk of ovarian hyperstimulation syndrome. DESIGN Retrospective series. SETTING Tertiary care infertility practice. PATIENT(S) Women who underwent SOV (n = 51) and IVF-ET (n = 93) treatment and who were at risk for OHSS. INTERVENTION(S) In SOV cycles, hMG was withheld (coasting) for >3 days before hCG administration, until follicular maturity was attained (> or = 3 follicles of > or = 18 mm) and E2 levels decreased. In IVF-ET cycles, either follicular maturity was attained before coasting (n = 63), allowing hCG administration after E2 levels decreased by >25%, or coasting occurred before follicular maturation (n = 30), necessitating the administration of additional hMG after coasting. MAIN OUTCOME MEASURE(S) Estradiol concentrations, follicle size, and pregnancy rates. RESULT(S) Estradiol concentrations usually rose for > or = 1 day after coasting began, then fell by > or = 25% while follicle numbers and mean diameters increased. No spontaneous LH surges occurred, although four SOV cycles were canceled because of excessive follicular development. Of the women who received hCG,11 of 47 (23% per cycle) conceived during SOV and 35 of 93 (37.6% per cycle) conceived during IVF-ET. Severe ovarian hyperstimulation syndrome developed in 1 woman who underwent IVF-ET. CONCLUSION(S) Coasting can safely rescue overstimulated SOV and IVF-ET cycles characterized by an excessive rise in E2 levels and/or numerous incompletely mature follicles.

Rescue intracytoplasmic sperm injection (ICSI)-salvaging in vitro fertilization (IVF) cycles after total or near-total fertilization failure

OBJECTIVE To evaluate the effectiveness of delayed oocyte reinsemination by ICSI (rescue ICSI) after total or near-total fertilization failure (</=25%) in IVF. DESIGN A retrospective clinical study. SETTING Non-hospital-based IVF program. PATIENT(S) Thirty IVF cycles with total fertilization failure and two cycles with </=25% initial fertilization. MAIN OUTCOME MEASURE(S) Fertilization and pregnancy rates after rescue ICSI. INTERVENTION(S) Rescue ICSI 19-22 hours after initial oocyte insemination. RESULT(S) A fertilization rate of 60.2% was achieved with rescue ICSI (141 of 234 oocytes, 29 of 32 patients). Of 30 patients with total fertilization failure, 27 had fresh transfers with rescue ICSI embryos. Two additional patients with </=25% initial fertilization had subsequent replacement of frozen-thawed rescue ICSI embryos. Six pregnancies resulted, including three singleton, one twin, one missed abortion, and one ectopic pregnancy (20.7%). One of the singleton pregnancies resulted from replacement of four frozen-thawed embryos and is the first known pregnancy achieved from cryopreserved rescue ICSI embryos. CONCLUSION(S) Rescue ICSI should be considered in the presence of total or near-total fertilization failure in IVF. Early application of rescue ICSI (19-22 hours after insemination) may be critical for establishing fertilization within an optimal window and producing viable embryos and pregnancies.

An ounce of prevention: outpatient management of the ovarian hyperstimulation syndrome

OBJECTIVE To evaluate a protocol of active outpatient management, including outpatient paracentesis and albumin administration, in women at risk for severe ovarian hyperstimulation syndrome (OHSS). DESIGN Prospective cohort. SETTING Freestanding IVF program. PATIENT(S) Thirteen women progressing from moderate to severe OHSS. INTERVENTION(S) Bed rest and home monitoring with intermittent outpatient paracentesis and albumin administration. MAIN OUTCOME MEASURE(S) Procedural outcomes and time to resolution of OHSS symptoms. RESULT(S) The initial paracentesis occurred 14.1 +/- 3.3 days after oocyte retrieval, removing 1,735 +/- 506 mL of ascitic fluid. Eleven women required a second paracentesis and five women required a third paracentesis over the next 8 days. Six women received albumin on seven occasions because of hypoalbuminemia. The onset of diuresis occurred 2.8 +/- 1.9 days and recovery occurred 7. 4 +/- 3.0 days after the first paracentesis. There were no hospitalizations for OHSS symptoms and no complications. All 13 women had viable intrauterine pregnancies. CONCLUSION Active outpatient intervention in the early stages of OHSS, including paracentesis and albumin administration, can avoid hospitalization while minimizing the progression and complications of OHSS.

Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study

OBJECTIVES To study the effect of GnRH agonist (GnRH-a) treatment on memory and to assess the role of psychological factors. DESIGN A randomized prospective study. SETTING An academic teaching hospital. PARTICIPANTS Women with endometriosis and infertility or endometriosis alone. MAIN OUTCOME MEASURES Memory Observation Questionnaire, Profile of Mood States, Health Concerns scale, a weekly diary of adverse effects. RESULTS Perceived memory functioning decreased during GnRH-a administration and by the final week of treatment 44% of women reported moderate to marked impairment in comparison to community norms. Prospective memory was most affected and withdrawal of GnRH-a treatment resulted in a return to normal memory functioning. Impairment was not related to excessive health concerns or mood changes and was uncorrelated with other adverse effects. CONCLUSIONS Memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized. Problems were temporary and more likely a result of rapid estrogen depletion than a consequence of mood, somatic distress, or personality factors.

Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization

OBJECTIVE To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF). DESIGN Randomized, prospective comparison in first cycles of IVF. SETTING University Hospital, a tertiary referral center offering assisted reproductive technologies. PARTICIPANTS Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial. RESULTS Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different. CONCLUSION A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate.

Transferring more embryos increases risk of heterotopic pregnancy

OBJECTIVES To analyze symptoms and signs that may distinguish heterotopic pregnancy from solely ectopic pregnancy (EP) after IVF. To determine if the number of embryos transferred is a risk factor for heterotopic compared with solely EP. DESIGN Retrospective cohort of 587 IVF pregnancies, 328 with distorted tubal anatomy. SETTING University Hospital, London, a referral center for Ontario provincial government-supported assisted reproductive technologies. PARTICIPANTS Couples undergoing IVF. INTERVENTION None. MAIN OUTCOME MEASURES Heterotopic pregnancy, solely EP, intrauterine pregnancy, and distorted pelvic anatomy. RESULTS Of 587 pregnancies, 7 were heterotopic pregnancies and 24 were solely EP, all in the subset of 328 women with distorted tubal anatomy. Symptoms, signs and time of diagnosis were not different between heterotopic and solely ectopic gestations. Compared with solely EP, heterotopic pregnancies were associated with transfer of more embryos. With four or more embryos transferred, the odds ratio for development of heterotopic versus solely ectopic gestation was 10.0. CONCLUSION Heterotopic pregnancy occurred in 2% of gestations after IVF, all in women with distorted tubal anatomy. Transfer of four or more embryos was a risk factor for heterotopic pregnancy.