Lynn M. Westphal

Incidence of monozygotic twinning with blastocyst transfer compared to cleavage-stage transfer

OBJECTIVE To evaluate the incidence of monozygotic twinning (MZT) in pregnancies conceived after blastocyst transfer compared to cleavage-stage transfer. DESIGN Retrospective study. SETTING University IVF program. PATIENT(S) All IVF patients with viable pregnancies conceived during a 4-year period. INTERVENTION(S) Blastocyst transfer or day 3 ET. MAIN OUTCOME MEASURE(S) Incidence of MZT assessed by transvaginal ultrasound. RESULT(S) There were 11 incidences of MZT in 197 viable pregnancies (5.6%) with blastocyst transfer compared to 7 of 357 viable pregnancies (2%) with day 3 ET. In 10 of 18 pregnancies, MZT was observed in the setting of a higher order multiple gestation (6 of 11 for blastocyst transfer and 4 of 7 for day 3 ET). In the day 3 ET group, assisted hatching or intracytoplasmic sperm injection (ICSI) did not increase MZT (4 of 213, 1.9%) compared to cycles without zona breaching (3 of 144, 2.1%). Similarly, in the blastocyst-transfer group, ICSI did not increase the incidence of MZT (4 of 74, 5.5% for ICSI and 7 of 123, 5.7% for non-ICSI IVF). CONCLUSION(S) Compared to day 3 ET, blastocyst transfer appears to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture.

Comparison of propofol with methohexital for outpatient anesthesia

Propofol is an intravenous anesthetic currently available for clinical investigative use. The intraoperative and postoperative effects of propofol were compared to methohexital when used as an adjuvant to nitrous oxide for outpatient anesthesia. Sixty healthy young women were randomly assigned to receive either methohexital, 1.5 mg/kg intravenously (IV), or propofol, 2.5 mg/kg IV, for induction of anesthesia. Both drugs produced transient cardiovascular and respiratory depression after induction. Maintenance of anesthesia consisted of either methohexital, 6 ± 2 mg/min, or propofol, 7 ± 2 mg/min (mean ± SD) by continuous infusion in combination with nitrous oxide, 70% in oxygen. Use of a propofol infusion was associated with lower blood pressures and heart rates during maintenance. Propofol was associated with fewer side effects (e.g., hiccoughing, nausea, and vomiting) intra- and postoperatively. Recovery times for awakening, orientation, and ambulation were consistently shorter with propofol. We conclude that propofol is a useful alternative to methohexital for induction and maintenance of outpatient anesthesia.

Is infertility a risk factor for female sexual dysfunction? A case-control study

OBJECTIVE To determine the impact of infertility on female sexual function. DESIGN A case-control study. SETTING Academic infertility and gynecology practices. PATIENT(S) One hundred nineteen women with infertility and 99 healthy female controls without infertility between the ages of 18 and 45 years were included in this study. INTERVENTION(S) Anonymous survey and Female Sexual Function Index. MAIN OUTCOME MEASURE(S) Female Sexual Function Index scores, frequency of sexual intercourse and masturbation, and sex-life satisfaction. RESULT(S) Twenty-five percent of our control group had Female Sexual Function Index scores that put them at risk for sexual dysfunction (<26.55), whereas 40% of our patients with infertility met this criterion. Compared with the control group, the patients with infertility had significantly lower scores in the desire and arousal domains and lower frequency of intercourse and masturbation. The patients with infertility retrospectively reported a sex-life satisfaction score that was similar to that of the controls before their diagnosis, whereas their current sex-life satisfaction scores were significantly lower than those of the controls. CONCLUSION(S) Women with a diagnosis of infertility were found to be at higher risk for sexual dysfunction on the basis of their Female Sexual Function Index scores compared with women without infertility. The interaction of sexual function and infertility is complex and deserves further study.

Interleukin-1 type I receptor messenger ribonucleic acid expression in human endometrium throughout the menstrual cycle *

OBJECTIVE To investigate the messenger ribonucleic acid (mRNA) expression of interleukin-1 (IL-1) type I receptor in the endometrial tissue of normal patients during the menstrual cycle. DESIGN Prospective longitudinal study. SETTING Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California. PATIENTS Twenty fertile women between 19 and 41 years of age underwent hysterectomy for benign reasons (n = 9) and laparoscopy for tubal ligation (n = 11). In all cases, endometriosis was not visualized. INTERVENTIONS Endometrial biopsy using the Novak curette was obtained at the time of surgery. MAIN OUTCOME MEASURE Total RNA extracted from unfractioned endometrial tissue was analyzed on Northern blots by using specific complementary deoxyribonucleic acid probes. RESULTS We found IL-1 type I receptor mRNA expression in endometrial tissue throughout the entire menstrual cycle. However, IL-1 type I receptor mRNA levels were significantly higher during both early and late luteal phases than follicular and midluteal phases. CONCLUSIONS Our results demonstrate the presence of the IL-1 system in the human endometrium and that the receptor is regulated throughout the menstrual cycle with a 4.1-fold increased expression of the IL-1 receptor gene in the early luteal phase compared with preovulatory endometrium.

Etiology of recurrent pregnancy loss in women over the age of 35 years

OBJECTIVE To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL). DESIGN Retrospective cohort study. SETTING Academic reproductive endocrinology and infertility clinic. PATIENT(S) Women>or=35 years old with >or=3 first trimester miscarriages. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (<or=2 losses) in women>or=35 years. RESULT(S) Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained. CONCLUSION(S) In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases.

Accuracy of day 3 criteria for selecting the best embryos

OBJECTIVE To assess the accuracy of day 3 morphologic criteria in identifying the best embryos. DESIGN Prospective observational study. SETTING University IVF program. PATIENT(S) One hundred cycles in women desiring blastocyst transfer who had > or =3 eight-cell embryos on day 3. INTERVENTION(S) On day 3, the embryologist chose the two embryos that would have been transferred that day. On day 5, embryos were examined to determine the best and second-best blastocysts. MAIN OUTCOME MEASURE(S) Accuracy of day 3 picks as measured in culture on day 5, outcome of nontransferred picks, and cryopreservation rate. RESULT(S) All cycles reached the blastocyst stage and 73% had cryopreservation. The mean number of blastocysts was 4.8 (3.2 on day 5 and 1.6 on day 6). Neither pick was chosen in 39% of cycles; one pick was transferred in 38%; and both picks were transferred in 23%. Of 116 nontransferred picks, 51 were frozen and 65 arrested, with both picks arresting in 9 cycles. The single best blastocyst was chosen from the picks in 39% of cycles. CONCLUSION(S) Morphologic criteria for cleavage-stage embryo selection may fall short when the transfer is limited to two embryos. Culture to blastocyst is warranted in this population to avoid high-order multiples and still be able to choose the two embryos with the highest implantation potential.

Ovarian stimulation for fertility preservation in patients with cancer

OBJECTIVE To evaluate controlled ovarian hyperstimulation (COH) in women with cancer compared with healthy women. DESIGN A retrospective cohort study. SETTING Academic assisted reproductive technology (ART) program. PATIENT(S) Fifty women undergoing oocyte retrieval before cancer treatment and 50 age-matched controls. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Number of oocytes and matured oocytes retrieved, number of fertilized oocytes, days of stimulation, dose of gonadotropins. RESULT(S) There were no significant differences in the number of oocytes retrieved (13 vs. 11.5), the number of matured oocytes retrieved (9.7 vs. 9.6), and the number of oocytes fertilized (7.4 vs. 6.8). However, the patients with cancer had a longer duration of stimulation (10.5 vs. 9.0 days) and higher total dose of gonadotropins (4,174 IU vs. 3,416 IU). CONCLUSION(S) In our study, reasonable ovarian response was achieved by women with cancer with increased doses of gonadotropins and a longer duration of stimulation.

Timing of Breast Cancer Treatments with Oocyte Retrieval and Embryo Cryopreservation

BACKGROUND Protecting future childbearing motivates young women with breast cancer to seek oocyte or embryo cryopreservation. Concerns about delays in cancer treatment may influence patients and practitioners considering these procedures. In this study, we compared timing of chemotherapy in women who underwent ovarian stimulation/oocyte retrieval (OR) and embryo cryopreservation with those who did not. STUDY DESIGN Eighty-two women younger than 40 years of age, who received adjuvant chemotherapy for breast cancer, were retrospectively identified. Nineteen underwent OR and 63 did not (CON). The timing of OR, surgery, and chemotherapy were compared with the time intervals between diagnosis and treatments in the CON group. RESULTS The mean ages of women were 33.7 years (OR group) and 35.2 years (CON group); 84.2% of OR and 25.4% of CON were nulliparous. The median time from initial diagnosis to reproductive endocrinology consultation was 30.1 days (range 4 to 133 days) and from referral to OR was 32 days (range 13 to 66 days). The median times from initial diagnosis to chemotherapy in OR versus CON groups were 71 days (range 45 to 161 days) and 67 days (range 27 to 144 days), respectively, p < 0.27. The median time interval from definitive operation to chemotherapy was similar in the two groups: 30 days (OR; range 14 to 100 days) and 29 days (CON; range 12 to 120 days), p < 0.79. CONCLUSIONS Fertility preservation is an important component of quality of life for young women with breast cancer. The time investment required for OR and cryopreservation is manageable and does not significantly prolong the time interval from diagnosis to start of adjuvant chemotherapy.

Stress and anxiety scores in first and repeat IVF cycles: a pilot study.

Background The role of stress in reproduction, particularly during treatment for infertility, has been of considerable interest; however, few studies have objectively measured stress and anxiety over the course of the IVF cycle or compared the experience of first-time and repeat patients. Methods This prospective cohort pilot study enrolled 44 women undergoing IVF at a university-based clinic to complete the State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and Infertility Self-Efficacy Scale (ISES) at three time points prior to ovarian stimulation (T1), one day prior to oocyte retrieval (T2), and 5–7 days post embryo transfer (T3). Results Mean STAI State scores were significantly elevated at all three time points (p<0.01). STAI State and PSS mean values did not change over time and did not differ in first-time vs. repeat patients. Self-efficacy (ISES) scores declined over time, with a greater decline for repeat patients. Of the 36 women who completed a cycle, 15 achieved clinical pregnancy. Using logistic regression modeling, all scores at T2 were correlated with pregnancy outcome with lower scores on the STAI State and PSS and higher scores on the ISES associated with higher pregnancy rates. Conclusions Stress and anxiety levels remained elevated across all cycles. Women with lower stress and anxiety levels on the day prior to oocyte retrieval had a higher pregnancy rate. These results emphasize the need to investigate stress reduction modalities throughout the IVF cycle.

Poor Prognosis with In Vitro Fertilization in Indian Women Compared to Caucasian Women Despite Similar Embryo Quality

Background Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos. Methodology/Principal Findings In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46–0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40–0.79) in the multivariate analysis. Conclusions/Significance Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed.