Michael J. Levy

Prognostic value of day 3 estradiol on in vitro fertilization outcome

OBJECTIVE To evaluate the prognostic value of day 3 E2 levels, independent of day 3 FSH levels, on responses to ovulation induction and subsequent pregnancy rates (PRs) in IVF-ET patients. DESIGN Prospective, observational. SETTING University-based tertiary care and private reproductive endocrine-infertility units. PATIENTS AND INTERVENTIONS A total of 225 patients underwent 292 IVF cycles with luteal phase GnRH agonist suppression and hMG stimulation. MAIN OUTCOME MEASURES We evaluated response and outcome data including age, day 3 FSH and E2 levels from a menstrual cycle before IVF, ampules of hMG used, maximum E2 level, cancellation rates, and clinical PR. RESULTS Despite similar age, number of ampules of hMG, and peak E2 levels, patients with an elevated E2 level (E2 > or = 80 pg/mL) (conversion factor to SI unit, 3.671) on day 3 of a cycle before IVF-ET achieved a lower PR per initiated cycle (14.8% versus 37.0%) and had a higher cancellation rate (18.5% versus 0.4%) compared with those with E2 levels < 80 pg/mL. Even when patients with elevated FSH levels (FSH > or = 15 mIU/mL) (conversion factor to SI unit, 1.00) were excluded (leaving 279 cycles), those with an elevated day 3 E2 still had a lower PR per initiated cycle (14.8% versus 38.9%) and maintained a higher cancellation rate (18.5% versus 0.4%). When the day 3 E2 was > or = 100 pg/mL there was a 33.3% cancellation rate and no pregnancies were achieved. CONCLUSION Patients who presented with an elevated day 3 E2 (> or = 80 pg/mL) in a cycle before IVF-ET had a higher cancellation rate and achieved a lower PR independent of FSH level. A day 3 E2 level, in addition to a day 3 FSH level, appears very helpful in prospectively counseling patients regarding cancellation risk and ultimate IVF-ET success.

The adverse effect of hydrosalpinges on in vitro fertilization pregnancy rates and the benefit of surgical correction.

OBJECTIVE To test the hypothesis that IVF-ET pregnancy rates (PRs) for patients with tubal factor infertility are decreased in patients with hydrosalpinges and that surgical correction reverses this effect. DESIGN Retrospective chart review. SETTING Private practice IVF-ET program. PATIENT(S) Patients (n = 160) undergoing 238 cycles of IVF-ET were stratified into groups based on the presence of hydrosalpinges and whether surgical correction had been performed. Patients >39 years old and patients with male factor infertility were excluded from the study. INTERVENTION(S) Patients with hydrosalpinges were offered surgical correction. MAIN OUTCOME MEASURE(S) Clinical pregnancy defined by an intrauterine gestational sac. RESULT(S) Patients with hydrosalpinges had significantly decreased implantation rates and PRs per transfer (2.8% and 8.5%, respectively) than patients with tubal factor infertility but without hydrosalpinges (15.7% and 38.6%). Surgical correction improved implantation rates and PRs in patients with prior failed cycles (16.1% and 37.5%) and in patients undergoing surgery before IVF-ET (21.8% and 51.7%). The type of surgery performed did not affect success rates in the small number of patients evaluated. CONCLUSION(S) The presence of a hydrosalpinx during an IVF-ET cycle results in significant decreases in implantation rates and PRs. Surgical treatment of hydrosalpinges before IVF-ET cycles improves implantation rates and PRs.

Blastocyst development after vitrification of multipronuclear zygotes using the Flexipet denuding pipette

The purpose of this study was to demonstrate the safety and efficacy of vitrification of human pronuclear stage (PN) embryos in the human assisted reproduction laboratory. Using single pronucleate (1PN) and three pronucleate (3PN) zygotes, the impact of vitrification in the Flexipet denuding pipette (FDP) as a carrier was assessed in terms of survival, embryonic development and blastocyst formation when compared according to the PN number, and unvitrified controls. A total of 65 1PN and 152 3PN zygotes were vitrified; after warming 82% (53/65) of 1PN and 90% (137/152) of 3PN survived. The overall percentage of warmed zygotes (1PN and 3PN) that cleaved and reached 2-cell stage did not differ (chi(2); P = 0.32) from the control groups (77%; 147/190 versus 85%; 115/136). In addition, when the cleavage behaviour was examined on day 3 for >or=4-cell stage, no significant differences (chi(2); P = 0.95) were observed between the vitrified group and the unvitrified control groups (74%; 109/147 versus 77%; 89/115). Comparing the developmental potential up to cavitation and blastocyst formation on day 5, the overall outcome of the vitrified PN was 31% compared with 33% for the controls (chi(2); P = 0.76). The simple vitrification protocol used in this study, and these data highlight the usefulness of vitrification using FDP as a consistent and effective cryopreservation method for pronuclear zygotes, and a suitable alternative to slow cryopreservation protocols.

Contribution of male age to outcomes in assisted reproductive technologies

OBJECTIVE To evaluate the relationship between male age and pregnancy outcome in donor oocyte assisted reproductive technology cycles. DESIGN Retrospective cohort. SETTING Private IVF center. PATIENT(S) A total of 1,392 donor cycles from 1,083 female recipients and their male partners. INTERVENTION(S) Oocyte donor cycles. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) Increasing male age was associated with semen parameters including volume and motility; however, male age was not observed to have a statistically significant association with likelihood of live birth in donor cycles after adjustment for female recipient age. CONCLUSION(S) When treatment cycle number and female recipient age were taken into account, male age had no significant association with pregnancy outcomes in assisted reproductive technology donor cycles in this study population.

Are good patient and embryo characteristics protective against the negative effect of elevated progesterone level on the day of oocyte maturation

OBJECTIVE To evaluate if an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration is associated with a decrease in live-birth rate in patients with a good prognosis. DESIGN Retrospective cohort study. SETTING Large, private, assisted reproductive technology (ART) practice. PATIENT(S) One thousand six hundred twenty fresh autologous ART cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Live-birth rate. RESULT(S) A total of 934 blastocyst and 686 cleavage-stage embryo transfer (ET) cycles were evaluated. Serum P levels were not associated with markers of oocyte or embryo quality, including fertilization, embryo stage at transfer, and embryos available for cryopreservation. Patient age, stage of ET, embryo quality, the number of embryos transferred, and P level on the day of hCG administration were all significantly associated with live birth. Higher P levels were associated with decreased odds of live birth for cleavage- and blastocyst-stage embryos, poor-fair and good-quality embryos, and poor- and high-responder patients. The nonsignificance of interaction tests of P levels with embryo stage, embryo quality, patient age, and ovarian response indicated that the relationship between P level and live birth was similar regardless of these factors. CONCLUSION(S) An elevated serum P level on the day of hCG administration was negatively associated with live birth, even in ETs with a good prognosis.

Does a frozen embryo transfer ameliorate the effect of elevated progesterone seen in fresh transfer cycles

OBJECTIVE To compare the effect of progesterone (P) on the day of trigger in fresh assisted reproduction technology (ART) transfer cycles versus its effect on subsequent frozen embryo transfer (FET) cycles. DESIGN Retrospective cohort study. SETTING Large private ART practice. PATIENT(S) Fresh autologous and FET cycles from 2011-2013. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) A paired analysis of patients who underwent both a fresh transfer and subsequent FET cycle and an unpaired analysis of data from all fresh transfer cycles and all FET cycles were performed. We analyzed 1,216 paired and 4,124 unpaired cycles, and P was negatively associated with birth in fresh but not FET cycles in all analyses. Interaction testing of P and cycle type indicated P had a different association with birth in fresh versus FET cycles. When P was ≥ 2 ng/mL at the time of trigger, live birth was more likely in FET versus fresh cycles in the paired analysis (47% vs. 10%), in the unpaired analysis (51% vs. 14%), and in unpaired, good blastocyst only transfer subgroup (51% vs. 29%). Live birth was similar in FET cycles, with P ≥ 2 ng/mL versus P < 2 ng/mL (51% vs. 49%). Conversely, live birth was lower in fresh cycles, with P ≥ 2 ng/mL versus P <2 ng/mL (15% vs. 45%). CONCLUSION(S) Elevated P levels on the day of trigger during the initial fresh cycle were negatively associated with live birth in the fresh transfer cycles but not in subsequent FET cycles. Freezing embryos and performing a subsequent FET cycle ameliorates the effect of elevated P on live-birth rates.

The predictive value of serum progesterone and 17-OH progesterone levels onin vitro fertilization outcome

PurposeIn order to identify parameters which predict prognosis for success with in vitro fertilization, 17-hydroxyprogesterone and progesterone levels were evaluated in 254 patients undergoing 296 in vitro fertilization cycles. Selected response and outcome data were recorded.ResultsPatients with intermediate values of serum progesterone (0.7–0.8 ng/ml) at the time of human chorionic gonadotropin administration achieved significantly higher pregnancy rates than patients with lower (<0.7 ng/ml) or higher (>0.8 ng/ml) levels. The clinical pregnancy rates were 46%, 31%, and 27% respectively (P = 0.02). There was no change in 17-hydroxyprogesterone concentration which predicted a higher pregnancy rate.ConclusionExcellent clinical pregnancy rates were noted in cycles with a progesterone level of 0.7–0.8 ng/ml, as well as good results in cycles above 0.8 ng/ml. There is therefore no reason to administer human chorionic gonadotropin at a smaller follicle size to prevent a rise in serum progesterone.

Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization

OBJECTIVE To compare corifollitropin alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF. DESIGN Phase 3 randomized, double-blind, noninferiority trial. SETTING Multicenter trial. PATIENT(S) A total of 1,390 women aged 35-42 years. INTERVENTION(S) A single injection of 150 μg of corifollitropin alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach ≥17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3. MAIN OUTCOME MEASURE(S) Vital pregnancy rate (PR), number of oocytes, and live birth rate. RESULT(S) Vital PRs per started cycle were 23.9% in the corifollitropin alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (-7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the corifollitropin alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (-0.2 to 1.2). The live birth rates per started cycle were 21.3% in the corifollitropin alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) -2.3% (-6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the corifollitropin alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups. CONCLUSION(S) Treatment with corifollitropin alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. CLINICAL TRIAL REGISTRATION NUMBER NCT01144416.

Oral contraceptive pretreatment in women undergoing controlled ovarian stimulation in ganirelix acetate cycles may, for a subset of patients, be associated with low serum luteinizing hormone levels, reduced ovarian response to gonadotropins, and early pregnancy loss.

Oral contraceptive pretreatment facilitated scheduling of pure FSH/GnRH antagonist cycles but in a small subset of patients was associated with low serum LH levels, reduced ovarian response, and early pregnancy loss. Supplementation with LH could be examined as a possible way to improve cycle outcome.

Healthy twin delivery after day 7 blastocyst transfer coupled with assisted hatching

OBJECTIVE To report a normal twin delivery after transfer of two fresh day 7 blastocysts. DESIGN Case report. SETTING Private infertility clinic. PATIENT(S) A 35-year-old woman with a 6-year history of primary infertility with significant pelvic adhesions. INTERVENTION(S) Review of individual IVF-ET therapy cycle. MAIN OUTCOME MEASURE(S) Full-term delivery after day 7 blastocyst transfer. RESULT(S) During the patients first IVF-ET cycle, the decision was made to undertake blastocyst transfer after extended culture. No blastocysts had formed until late on day 6, by which time the patient had been hospitalized with a renal stone. Subsequently, on day 7, the patient was asymptomatic and presented for embryo transfer, and after assisted hatching, two expanded blastocysts were transferred to her uterus under ultrasound guidance. After confirmation of implantation of a viable twin, pregnancy was uneventful with no obstetrical complications, and a dizygotic twin was delivered vaginally at 38 weeks of gestation. CONCLUSION(S) Few reports have been made regarding viability of more slowly developing blastocysts; however, this case indicates that blastocysts that did not fully expand until day 7 of extended in vitro culture are still able to implant after superovulation and IVF-ET therapy. Assisted hatching of these embryos may have been beneficial in achieving this successful outcome by hastening the blastocyst hatching, allowing more rapid contact with the endometrium.