John L. Frattarelli

A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles

OBJECTIVE To determine the predictive value and define threshold values for basal antral follicle count in patients undergoing IVF. DESIGN Prospective cohort analysis. Tertiary care center. Two hundred eighty-nine patients. Transvaginal ultrasonography before starting gonadotropin administration. MAIN OUTCOME MEASURES Number of oocytes retrieved, basal hormone levels, and cycle outcomes. RESULTS Pregnant patients had significantly more antral follicles (13.8 +/- 7.5 vs. 12.4 +/- 10.0). Patients in whom cycles were canceled had significantly fewer antral follicles (7.6 +/- 4.8 vs. 13.7 +/- 8.8). Antral follicle count significantly correlated with most prestimulation and poststimulation IVF variables. Threshold analysis demonstrated a lower pregnancy rate (23.5% vs. 57.6%) and a higher cancellation rate (41% vs. 6.4%) associated with having four or fewer antral follicles. CONCLUSION(S) The basal antral follicle count identified patients who responded poorly to IVF stimulation. Having four or fewer antral follicles was associated with a high cancellation rate (41%) and, in patients without a cancelled cycle, a low pregnancy rate (23%). However, no antral follicle count absolutely predicted pregnancy or cycle cancellation.

Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System

OBJECTIVE To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004-2006. DESIGN Retrospective cohort. SETTING Clinic-based data. PATIENT(S) The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Clinical intrauterine gestation (presence of gestational sac) and live birth (>or=22 weeks gestation and >or=300 g birth weight). RESULT(S) Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters. CONCLUSION(S) Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies.

Assessing ovarian response: antral follicle count versus anti-Müllerian hormone

Oocyte number and quality decline with age; however, fertility varies significantly even among women of the same age. Various measures have been developed to predict response to ovarian stimulation and reproductive potential. Evaluation of ovarian reserve can identify patients who may experience poor response or hyper-response to exogenous gonadotrophins and can aid in the personalization of treatment to achieve good response and minimize risks. In recent years, two key methods, antral follicle count (AFC), an ultrasound biomarker of follicle number, and the concentration of serum anti-Müllerian hormone (AMH), a hormone biomarker of follicle number, have emerged as preferred methods for assessing ovarian reserve. In this review, a live debate held at the American Society for Reproductive Medicine 2013 Annual Meeting is expanded upon to compare the predictive values, merits, and disadvantages of AFC and AMH level. An ovarian reserve measure without limitations has not yet been discovered, although both AFC and AMH have good predictive value. Published evidence, however, as well as the objectivity and potential standardization of AMH level and the convenience of testing any time throughout the menstrual cycle, leans towards AMH level becoming the gold-standard biomarker to evaluate ovarian reserve and predict ovarian response to stimulation.

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.

A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles

OBJECTIVE To compare embryo and birth data in cryopreserved-thawed blastocyst-stage ET cycles between natural endogenous hormone cycles and exogenous hormone stimulation cycles. DESIGN Retrospective cohort analysis. SETTING Large academic assisted reproductive technology center. PATIENT(S) One thousand three hundred ninety-one patient cycles undergoing frozen-thawed blastocyst-stage ET cycles. MAIN OUTCOME MEASURE(S) Live-birth rate. INTERVENTION(S) The synthetic protocol used GnRH agonist followed by estrogen and P. The natural protocol used monitoring and post-transfer P. RESULT(S) The patients in the two protocols had similar baseline characteristics. Multiple linear regression showed the synthetic protocol to have a higher live-birth rate (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.02-2.09). In patients having two embryos transferred, the synthetic stimulation protocol resulted in a higher live-birth rate per cycle start (32.3% vs. 20.4%; relative risk [RR], 1.58; 95% CI, 1.22-2.06). Similarly, patients with one or two embryos transferred who had additional cryopreserved blastocysts available also had a higher live-birth rate per cycle start (36.1% vs. 12.1; RR, 2.98; 95% CI, 1.16-7.63). CONCLUSION(S) The synthetic hormone protocol was associated with a higher live-birth rate when compared with a natural cycle protocol for frozen-thawed blastocyst-stage ET cycles. This improvement persisted when analysis was controlled for cycle cancellation. The synthetic stimulation protocol for frozen-thawed embryo cycles offers improved outcome results for patients.

IMPACT OF BODY MASS INDEX ON IN VITRO FERTILIZATION OUTCOMES

AbstractPurpose: To determine if body mass index (BMI) impacts IVF outcome. Methods: Retrospective, cohort study. Main outcome measure was number of oocytes obtained. Results: BMI did not correlate with the prestimulation parameters. There was a significant positive correlation between BMI and the number of follicles on ultrasound prior to egg retrieval. A threshold analysis revealed a significant change in parameters at a BMI > 24 kg/m2. Patients with BMI > 24 kg/m2 demonstrated a significant increase in the number of follicles after stimulation (p = 0.03) and a comparative decrease in the number ampules of gonadotropins used (p = 0.04) and days of stimulation required (p = 0.01). Conclusion: These data demonstrated that an elevated BMI significantly correlates with the number of follicles, days of stimulation, and number of ampules of gonadotropins used. Further correlation to an actual increase in number of oocytes and pregnancy rates may be limited by insufficient power in this study.

A luteal estradiol protocol for anticipated poor-responder patients may improve delivery rates

OBJECTIVE To compare IVF data and outcomes between a standard protocol and a luteal phase E(2) protocol. DESIGN Retrospective cohort analysis. SETTING(S) Large academic assisted reproduction technologies center. PATIENT(S) Fifty-seven infertile patients with a history of poor response to IVF stimulation and 228 matched control patients. INTERVENTION(S) IVF with a standard protocol or a luteal phase E(2) protocol. MAIN OUTCOME MEASURE(S) Live-birth rates. RESULT(S) Patients in the luteal E(2) protocol required more days of stimulation and total gonadotropins and had higher peak E(2) levels when compared with the control group. The luteal E(2) protocol showed a greater percentage of embryos with >or=7 cells on day 3. A trend toward improved delivery rates was seen in the luteal E(2) protocol (28.1% vs. 22.4%; relative risk, 1.25, 0.78-2.03). CONCLUSION(S) A luteal E(2) protocol results in improved day 3 embryo development as demonstrated by the percent of embryos at the >or=7-cell stage. Likewise, the luteal E(2) protocol may ultimately improve pregnancy outcomes for patients with poor response to IVF stimulation.

The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle

AbstractPurpose: To prospectively evaluate serum and follicular fluid leptin, estradiol, and progesterone levels during in vitro fertilization. Methods: Prospective observational study measuring serum levels at six points during the IVF cycle and follicular fluid at the time of retrieval. Results: Serum leptin and estradiol levels both significantly increased for the individual patients during the IVF stimulation process. None of the leptin levels differed based on pregnancy outcome. BMI significantly correlated with all leptin levels. Follicular fluid estradiol correlated with serum estradiol only in pregnant patients (r = 0.97, p<0.01) and was unrelated in non-pregnant patients (r=−0.15, p=0.81). Conclusion: Serum and follicular leptin levels are highly correlated. Leptin levels increase during the IVF cycle and vary between patients based on maternal BMI, but do not correlate with other serum hormone levels or pregnancy outcome. Pregnancy outcome success was reflected in the relationship between follicular fluid and serum levels of estradiol, independent of leptin levels.

Live birth sex ratios are not influenced by blastocyst-stage embryo transfer

OBJECTIVE To analyze the sex ratio of infants born after blastocyst-stage transfer of embryos with normal preimplantation FISH genetic screening. DESIGN Retrospective cohort analysis. SETTING Large academic assisted reproductive technology center. PATIENT(S) Two hundred twenty-eight patients undergoing fresh IVF cycle with blastocyst transfer. INTERVENTION(S) Preimplantation genetic screening for sex complement. MAIN OUTCOME MEASURE(S) Sex ratio in liveborn infants following blastocyst transfer. RESULT(S) One thousand thirteen embryos were normal by preimplantation genetic screening of chromosomes 13, 15, 16, 17, 18, 21, 22, X, and Y. Four hundred ninety-eight normal embryos were transferred to 228 patients with an overall live birth rate of 41.7%. Transferred blastocysts were selected based upon morphologic assessment. When controlling for the sex of the blastocyst embryo, there was no difference in the male-to-female delivery rate per embryo transferred (27.3% vs. 21.4%) (relative risk =1.28, confidence interval 0.93-1.74). Of the live births 51.7% were male and 48.3% were female (P=.61). Subanalysis revealed no difference in male-to-female delivery rates in groups with a 1:1 ratio of male:female embryos transferred, a non 1:1 ratio transferred, or single-sex transfers. CONCLUSION(S) Blastocyst-stage embryo transfer does not influence the live birth sex ratio of embryos with normal preimplantation FISH genetic screening.

Adjuvant therapy enhances endometrial receptivity in patients undergoing assisted reproduction

Adjuvant therapies are often used to enhance endometrial thickness during IVF. This retrospective cohort analysis investigated if women undergoing oocyte donation cycles with sonographic evidence of endometrial insufficiency benefit from adjuvant medicaltherapy. Infertile patients received 503 mock cycles followed by 503 anonymous oocyte donation cycles. One hundred and twenty-three patients received adjuvant therapy during a donor oocyte cycle. Patients who had a mock endometrial thickness > or = 8 mm experienced a significant decrease in endometrial thickness with the donor oocyte cycle regardless of the use of adjuvant therapy (P < 0.001). In contrast, those patients with a mock endometrial thickness < 8 mm experienced a significant increase in donor oocyte cycle endometrial thickness regardless of adjuvant therapy use (P < 0.001). The patients with a mock endometrial thickness < 8 mm experienced a significant improvement in pregnancy rates when taking adjuvant therapy (87.7 versus 73.5%, P < 0.05). Adjuvant therapy significantly improved both pregnancy (87.8 versus 76.8%, P < 0.01) and live birth rates (74.8 versus 63.7%, P < 0.05) in the entire patient population. While the use of adjuvant therapy did not significantly improve ultrasonographic endometrial thickness, it did improve outcome rates.