Adrian Shulman

Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: A randomized prospective study

BACKGROUND The aim of this study was to evaluate the effect of dehydroepiandrosterone (DHEA) supplementation on in vitro fertilization (IVF) data and outcomes among poor-responder patients. METHODS A randomized, prospective, controlled study was conducted. All patients received the long-protocol IVF. Those in the study group received 75 mg of DHEA once a day before starting the next IVF cycle and during treatment. RESULTS Thirty-three women with significantly diminished ovarian reserves were enrolled, 17 in the DHEA group and 16 in the control group. The 33 patients underwent 51 IVF cycles. The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P = 0.09) and improved embryo quality during treatment (P = 0.04) between first and second cycles. Patients in the DHEA group also had a significantly higher live birth rate compared with controls (23.1% versus 4.0%; P = 0.05), respectively. Six of seven deliveries were among patients with secondary infertility (P = 0.006). CONCLUSION Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment. Clinicaltrials.gov: NCT01145144.

Relationship between embryo morphology and implantation rate after in vitro fertilization treatment in conception cycles

OBJECTIVE To investigate the relationship between the embryo number and morphology in conception cycles and the incidence of multiple pregnancies. DESIGN The study is based on information received from a computerized data base. SETTING In Vitro Fertilization Unit, Sapir Medical Center, Kfar Saba, Israel. PATIENTS A total of 117 consecutive pregnancies resulted from replacement of fresh embryos in our IVF-ET program. MAIN OUTCOME MEASURES The impact of embryo quality, as assessed by morphological parameters, on the multiple pregnancy rate (PR). RESULTS Implantation rates positively correlated with the number and the quality of transferred embryos. However, no multiple pregnancies occurred when only two embryos were replaced. There were no multiple pregnancies when only embryos of low quality (grades 1 and 2) were transferred. Furthermore, there was no correlation between the number of replaced embryos of poor quality and the rate of implantation. The multiple PR increased from 10% when a mixture of high and low quality embryos were transferred to 30.76% when only embryos of highest quality were transferred. CONCLUSION The implantation rate of transferred embryos is directly correlated with the morphological scoring. The results of the study suggest that the number of embryos transferred should be balanced against their morphological quality to reduce the rate of multiple pregnancies.

The impact of different types of anesthesia on in vitro fertilization-embryo transfer treatment outcome

ObjectiveOur objective was to evaluate retrospectively the influence of different types of anesthesia on the outcome of ovum retrieval.MethodsSedation combined with local anesthesia was used on 120 occasions (Group I), epidural block in 139 ovum retrievals (Group II), and general anesthesia in 173 cycles (Group III).ResultsNo differences were found in embryo yield or number or the quality of the embryos transferred. Of 99 pregnancies achieved, 66 live deliveries were recorded. Significantly lower clinical pregnancy rates were found in Group III (14.5%) compared with Group II (23.7%; P= 0.018) or Group I (25.8%; P=0.0074). Highly significant differences were found in the delivery rates between Group HI (8.7%), Group II (20.11%; P=0.0017), and Group I (19.2%; P=0.0043).ConclusionThe use of general anesthesia, especially nitrous oxide, for oocyte retrieval has an adverse effect on IVF outcome. This deleterious effect manifests itself only after embryo transfer and leads to lower pregnancy and delivery rates.

The significance of an early (premature) rise of plasma progesterone in in vitro fertilization cycles induced by a long protocol of gonadotropin releasing hormone analogue and human menopausal gonadotropins

AbstractObjective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome Methods: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) (“long protocol”). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: <0.9 ng/ml (Group A), 1–2 ng/ml (Group B), and >2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration. Results: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P<0.005). The embryo implantation rate was found to be negatively correlated with the PP levels on the day of hCG administration. In contrast, there was an opposite trend between PP levels and the chance of conception in 30 pregnancies achieved by egg donation. Conclusions: Since premature luteinization is very unlikely to occur under the conditions of this study, our findings suggest that an early PP rise has a negative impact on endometrial receptivity but not on egg and embryo quality.

Sperm Motility Is a Major Determinant of Pregnancy Outcome Following Intrauterine Insemination

Purpose:Our purpose was to assess whether one or more sperm parameters have predictive value for the outcome of intrauterine insemination treatment.Methods:Infertile couples whose normoovulatory and normomechanical female partners underwent superovulation and intrauterine insemination were investigated. The semen profile of the male partner was discounted. In 160 couples, 544 cycles were obtained, resulting in 59 ongoing pregnancies (10.84%/cycle, 36.87%/patient).Results:The only parameter found to be significantly correlated with a positive outcome was the degree of sperm motility following preparation for intrauterine insemination. Close to half (47.5%) of the couples with a very good or an excellent degree of sperm motility conceived, whereas only 8.3% of those patients who had poor or fair sperm motility conceived. None of the semen characteristics, such as volume, count, percentage motility, or percentage normal morphology, were found to correlate with cycle outcome. Although there was a progressive increase in the pregnancy rate with an increase in the total number of motile sperm inseminated, it did not reach significance. Seventy percent of the pregnancies were achieved within a maximum of three treatment cycles. The spermatogram is not accurate enough as a prognostic factor for treatment outcome.Conclusions:The degree of sperm motility, after appropriate preparation for intrauterine insemination, is the only parameter to be correlated with treatment outcome. For couples with a normal female partner, we suggest a maximum of three treatment cycles of induction of ovulation and intrauterine insemination, whenever good progressive motile sperm is obtained after suitable preparation. For cases with poor sperm progression, we suggest appropriate couple counseling and that an alternative assisted reproduction procedure be taken into consideration.

Modified Natural Cycle Using GnRH Antagonist Can Be an Optional Treatment in Poor Responders Undergoing IVF

Purpose: To investigate the efficacy of gonadotrophin-releasing hormone (GnRH) antagonist supplementation during natural cycles in poor responders undergoing IVF-ET treatment.Methods: We retrospectively evaluated 540 cycles of 433 suitable patients who were divided by treatment protocol into modified natural, antagonist, and long agonist groups. There were 52 modified natural cycles with GnRH antagonist supplementation, 200 stimulated cycles with GnRH antagonist, and 288 long GnRH agonist cycles. Cycle characteristics and treatment outcomes were compared between the groups.Results: The mean number of oocytes retrieved in the modified natural group was significantly lower than in the stimulated antagonist and long agonist groups (1.4± 0.5 vs. 2.3± 1.1 and 2.5± 1.1, respectively, p < 0.05). The respective implantation and pregnancy rates were 10% and 14.3%, 6.75% and 10.2%, and 7.4% and 10.6%. Cycle outcome and cycle properties were similar.Conclusions: Modified natural IVF cycle with GnRH antagonist supplementation is a feasible alternative to ovarian stimulation protocols in poor responders.

FACTORS PREDICTING IVF TREATMENT OUTCOME: A MULTIVARIATE ANALYSIS OF 5310 CYCLES

The objective of this study was to analyse factors predicting live birth rate following IVF. A computerized database of 1928 women who underwent 5310 consecutive IVF cycles in a single IVF unit was evaluated. Data on the womens age, number of retrieved oocytes, performance of intracytoplasmic sperm injection (ICSI), aetiology of infertility, number of transferred embryos and option of choosing embryos for transfer were evaluated. There were 1126 pregnancies that resulted in 689 live births. Transferring two embryos doubled the chances of delivery compared with one embryo, but transferring three embryos was not significantly superior to two embryos. Moreover, following a three-embryo transfer, the multiple delivery rates were significantly higher (P < 0.01) compared with transferring two embryos. Optimal delivery rates were observed in women aged 26-30 years, with gradual decline with advanced age. The performance of ICSI resulted in higher delivery rates compared with conventional insemination. According to these data, the best live birth results following IVF treatment were achieved when the maternal age was 26-30 years, in couples with male factor infertility undergoing ICSI, and when two embryos were transferred.

The aged uterus: multifetal pregnancy outcome after ovum donation in older women

BACKGROUND We aimed to investigate whether multifetal pregnancies are at risk of more pregnancy complications in women of advanced age after ovum donation. METHODS Pregnancy outcome in women after ovum donation aged 40 and above was extracted. Labor and delivery data as well as antenatal records of women carrying twins were compared with those of singletons, as well as to a control group of all twin pregnancies delivered at Sheba Medical Center during 2007. RESULTS One hundred and twenty-five women after ovum donation aged > or = 40 were studied. Of those, 42 women carried twin pregnancies and 83 carried singletons. The 42 women carrying twins comprised the study group and were compared with 417 control women with twins. Mean maternal age was 49.2 +/- 4.3 years. Hypertensive complications (50%), diabetes in pregnancy (31%) and hospitalization in pregnancy (69%) were all extremely high in the study group. Mean gestational age at delivery was lower for the study group compared with controls (35.2 +/- 2.3 versus 35.7 +/- 2.6 weeks), with 35.7% of infants in the study group born < or = 34 weeks gestation compared with 21.8% of controls, (OR: 1.99, 95% CI: 1.02-3.89). Mean birthweight was also significantly lower for study group infants compared with controls, with 77% of study infants born <2500 g compared with only 60% of controls (OR: 2.22, 95% CI: 1.3-3.77). CONCLUSIONS Pregnancy in advanced maternal age women after ovum donation carrying twins is associated with significant maternal and fetal complications, with increased risks of prematurity and lower birthweight. Possibly, the aged uterus is less suitable for carrying a multifetal pregnancy than a younger uterus. Therefore, the alternative of transferring a single, good-quality embryo should be the preferred option.

Outcome of In Vitro Fertilization and Intracytoplasmic Injection of Epididymal and Testicular Sperm Extracted from Patients with Obstructive and Nonobstructive Azoospermia

OBJECTIVE To evaluate IVF outcome after epididymal and testicular sperm retrieval in patients with obstructive or nonobstructive azoospermia. DESIGN Retrospective clinical analysis. SETTING Public university-affiliated IVF unit. PATIENT(S) One hundred twenty-three azoospermic patients (178 cycles). INTERVENTION(S) Sixty-three patients (103 cycles) with obstructive azoospermia (group 1) underwent either epididymal or testicular sperm retrieval, and 60 patients (75 cycles) with nonobstructive azoospermia (group 2) underwent testicular sperm retrieval combined with IVF treatment. Mature oocytes were fertilized using intracytoplasmic sperm injection. After sperm preparation, supernumerary spermatozoa were cryopreserved. MAIN OUTCOME MEASURE(S) Oocyte fertilization rate and clinical pregnancy rate (PR). RESULT(S) The oocyte fertilization rate was 48.4% (534/1,104) in group 1 and 41.5% (312/751) in group 2 (not significant [NS] difference). A total of 100 cycles (97.1%) and 62 cycles (82.7%) in the obstructive and nonobstructive groups, respectively, had embryos for replacement (NS difference). The clinical PRs per ET cycle were 24% (24/100) and 17.7% (11/62) in the two groups, respectively. Oocyte fertilization rates, when fresh (46.4%) or frozen-thawed (41.8%) spermatozoa were used, were not significantly different in the two groups. The PR when fresh sperm were used was 23.6% (30/127), versus 14.3% (5/35) when frozen sperm were used (NS difference). The PR for women aged < or = 35 years was similar to that for women >35 years of age (20.7% or 29/140 and 18.2% or 4/25, respectively). CONCLUSION(S) Epididymal and testicular sperm obtained in azoospermic patients can fertilize oocytes successfully and may lead to high fertilization rates and PRs. Freezing of these spermatozoa does not reduce the outcome of treatment significantly.

Cumulative live birth rate following in vitro fertilization: Study of 5310 cycles

Most previous studies that calculated cumulative delivery rates following in vitro fertilization (IVF) treatments were limited in the number of cycles and the implementation of intracytoplasmic sperm injection (ICSI). Therefore, we assessed the yield of high-order consecutive IVF treatments (up to 14 consecutive cycles) with and without ICSI. Data from IVF cycles performed in a single center were retrieved from a computerized database. A total of 5310 cycles among 1928 patients were evaluated and cumulative delivery rates until the first delivery were calculated using life-table analyses. There were 1126 pregnancies resulting in 689 live births. Cumulative delivery rates reached 87% following 14 consecutive cycles. Cumulative delivery rates were higher following ICSI compared with cycles without (92.7% vs. 85.4%). In conclusion, each treatment cycle increased the cumulative delivery rate, resulting in a rate of 87% after 14 consecutive cycles. The introduction of ICSI resulted in the highest cumulative rates.