M.A.B. Melo

Female obesity impairs in vitro fertilization outcome without affecting embryo quality

OBJECTIVE To compare embryo quality and reproductive outcome in our IVF program according to the womens body mass index (BMI). DESIGN Retrospective study. SETTING University-affiliated infertility clinic, between January 2001 and April 2007. PATIENT(S) Women undergoing a total of 6,500 IVF-intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S) Six thousand five hundred IVF-ICSI cycles were included and divided into four groups: lean (<20 kg/m(2); n = 1,070; 16.5%); normal (20-24.9 kg/m(2); n = 3,930; 60.5%); overweight (25-29.9 kg/m(2); n = 1,081; 16.6%); and obese (> or =30 kg/m(2); n = 419; 6.4%). MAIN OUTCOME MEASURE(S) Comparison of embryo quality and reproductive outcome (implantation, pregnancy, miscarriage, and live birth rates) among BMI groups. RESULT(S) No difference in insemination procedure, fertilization rate, day of ET, mean number of transferred and cryopreserved embryos, percentage of blastocyst transfers, or embryo quality on day 2 and 3 was found among groups. However, implantation, pregnancy, and live birth rates were poorer in obese women. In fact, pregnancy and live birth rates were reduced progressively with each unit of BMI (kilograms per square meter) with a significant odds ratio of 0.984 (95% confidence interval 0.972-0.997) and 0.981 (95% confidence interval 0.967-0.995), respectively. In addition, the cumulative pregnancy rate after four IVF cycles was reduced as BMI increased. CONCLUSION(S) Female obesity impairs IVF outcome, but embryo quality is not affected, pointing to an alteration in the uterine environment.

Cigarette smoking and reproductive function

Purpose of review To perform a systematic review of the literature on the relationship between cigarette smoking and reproductive function. Whenever possible, this review is focused on the most recently published studies (mainly the past 2 years). Nevertheless, in many instances older literature was too relevant not to be taken into account. Recent findings Tobacco compounds exert a deleterious effect on the process of ovarian follicle maturation. This effect is expressed by worse in-vitro fertilization parameters in cycles performed on women with smoking habits. Also, uterine receptiveness is significantly altered by the smoking habit. In men, cigarette smoking reduces sperm production, increases oxidative stress, and DNA damage. Spermatozoa from smokers have reduced fertilizing capacity, and embryos display lower implantation rates. Even in-utero exposition to tobacco constituents leads to reduced sperm count in adult life. Summary A strong body of evidence indicates that the negative effect of cigarette smoking on fertility comprises fairly every system involved in the reproductive process. Couples in reproductive age should be strongly discouraged to smoke.

Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome.

OBJECTIVE To determine whether luteal phase endometrial transcriptome is altered in obese women during the window of implantation (WOI), considering the presence of infertility, fat distribution and association with polycystic ovary syndrome (PCOS). DESIGN Prospective study. SETTING University-affiliated infertility clinic, between May 2007 and March 2009. PATIENT(S) One control group of women with normal weight (n=4), and four study groups of obese women (n=6 each one) according to the association with infertility, PCOS, and ovarian stimulation. INTERVENTION(S) The endometrium was biopsied 7 days after LH surge or hCG administration in 28 women. MAIN OUTCOME MEASURE(S) Endometrial gene expression during the WOI. RESULT(S) One hundred and fifty-one genes were dysregulated in obese groups compared with controls. This dysregulation was more pronounced when infertility was associated. The biologic processes of these genes belonged mainly to development and regulation of different biological functions such as transcription and biosynthesis. The molecular functions overrepresented were transcription and peptide receptor activity. The endometrium of obese women with PCOS showed dysregulated genes related to biologic processes such as development, morphogenesis, and the immune system, as well as different molecular functions such as protein binding, binding, growth factor activity, and carboxylic acid transmembrane transporter activity. Some of these genes have been previously related to implantation and unexplained infertility. CONCLUSION(S) Obese women present a different endometrial gene expression than controls during the WOI, which is more pronounced when infertility or polycystic ovary syndrome are associated.

Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development

BACKGROUND Ovarian stimulation regimens for in vitro fertilization seem to have a deleterious effect on oocyte quality and embryo aneuploidy in a dose-dependent manner. This study aims to test the influence of gonadotrophin doses on embryo aneuploidy rates. METHODS A total of 32 young oocyte donors with a high response to ovarian stimulation, were included in the study. Two subsequent stimulation treatments were performed in each donor: first, a standard dose cycle using a 225 IU starting dose of recombinant FSH (r-FSH) and secondly, a reduced dose cycle with a starting dose of 150 IU r-FSH. In both cycles, GnRH agonist co-treatment was used for down-regulation. Ovarian response, embryo development and aneuploidy for chromosomes 13, 15, 16, 17, 18, 21, 22, X and Y were the main outcomes of the study. RESULTS A total of 22 donors completed both treatments with different gonadotrophin doses. In the remaining 10 donors, the reduced dose cycle was cancelled due to low ovarian response. In those donors who completed both regimens, significant increases in rates of fertilization and chromosomally normal blastocysts were observed in the reduced dose cycle. No differences were observed in pregnancy and implantation rates in recipients who received oocytes from standard and reduced doses cycles. CONCLUSIONS Despite the limited numbers in our study, we can conclude that in high responder donors, a decrease in the gonadotrophin dose could improve fertilization rates and embryo quality. However, due to the reduced oocyte numbers with lower doses, a similar reproductive outcome in terms of live births would be expected.

Antral follicle count (AFC) can be used in the prediction of ovarian response but cannot predict the oocyte/embryo quality or the in vitro fertilization outcome in an egg donation program.

OBJECTIVE To verify whether the antral follicle count (AFC) could predict ovarian response, oocyte/embryo quality, and IVF outcome. DESIGN Prospective study. SETTING Instituto Universitario-Instituto Valenciano de Infertilidad, Valencia, Spain. PATIENT(S) One thousand seventy-four donors and 975 oocyte recipient cycles. INTERVENTION(S) Controlled ovarian hyperstimulation (COH), endometrial preparation, IVF/intracytoplasmic sperm injection, ET. MAIN OUTCOME MEASURE(S) COH and oocyte/embryo quality parameters and IVF outcome. RESULT(S) We observed lower E(2) levels and fewer mature retrieved oocyte numbers among donors who showed an AFC that was <10. These donors also showed significantly higher cancellation and no-donation rates; poor and/or insufficient response was the principal cause (82%). However, there were no differences among the groups regarding embryo development parameters and IVF outcome. CONCLUSION(S) AFC is a noninvasive and simple tool that can improve the oocyte donors selection of an egg donation program. This study suggests that AFC is a good predictor of ovarian response but cannot be used to predict oocyte/embryo quality or IVF outcome.

Cigarette smoking and IVF

The goal of this article is to present a thorough review of the literature concerning the relationship between cigarette smoking and IVF cycle outcome, as well as the possible mechanisms through which tobacco constituents affect these cycles. Cigarette smoke affects spermatozoa structure and function; sperm DNA is damaged by tobacco compounds. Spermatozoa from smokers have reduced fertilizing capacity and embryos display lower implantation rates. Ovarian aging is accelerated in smokers and oocyte number and maturation are negatively affected by cigarette smoke. Clinical parameters of IVF cycle outcome are worse in female smokers. This is also the consequence of impaired uterine receptiveness.

A prospective, randomized, controlled trial comparing three different gonadotropin regimens in oocyte donors: ovarian response, in vitro fertilization outcome, and analysis of cost minimization

OBJECTIVE To compare the efficacy of three different gonadotropin regimens in an oocyte donation program. The analysis of cost minimization also was evaluated. DESIGN Prospective, randomized, controlled study. SETTING Instituto Universitario-IVI, Valencia, Spain. PATIENT(S) One thousand twenty-eight donors undergoing a GnRH agonist protocol were assigned randomly to one of three groups: group 1 (n=346), only recombinant FSH (rFSH); group 2 (n=333), only highly purified menotropin (HP-hMG); and group 3 (n=349), rFSH plus HP-hMG. One thousand seventy-nine oocyte recipients. INTERVENTION(S) Controlled ovarian stimulation. MAIN OUTCOME MEASURE(S) Controlled ovarian stimulation parameters, IVF outcome, and cost analysis. RESULT(S) No differences were found among the groups with respect to days of stimulation, gonadotropin dose, final E2 and P levels, number of oocytes retrieved, and cancellation rate. Similarly, there were no differences among the groups in terms of embryo development parameters. Moreover, implantation, pregnancy, and miscarriage rates with the three regimens were similar. However, the cost of rFSH was greater than that of the other protocols. CONCLUSION(S) This study suggests that in the GnRH agonist protocol the three different gonadotropin regimens evaluated herein are equally effective. Protocols using HP-hMG would appear to be the best in terms of cost-effectiveness in an oocyte donation program.

GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles: a randomized controlled trial

OBJECTIVE To assess whether GnRH agonist administration in the luteal phase improves pregnancy outcome in intrauterine insemination (IUI) cycles. DESIGN Single-center, randomized, single-blind, placebo-controlled trial. SETTING University-affiliated infertility clinic, between February 2005 and December 2007. PATIENT(S) Three hundred forty-four women undergoing IUI owing to mild to moderate male factor or donor sperm indication. INTERVENTION(S) Random administration to either a single subcutaneous injection of 0.1 mg triptorelin (group A; n=172) 8 days after hCG administration, or solvent only (group B; n=172) at the same time. MAIN OUTCOME MEASURE(S) Pregnancy rate was the primary outcome measure considered for assessing the role of triptorelin administration at the time of implantation. Clinical pregnancy, miscarriage, and ongoing pregnancy rates were the secondary outcome measures. RESULT(S) No differences were detected between the groups regarding clinical, seminal, or ovarian stimulation parameters. Pregnancy rate per randomized patient was similar in both groups (22.7% vs. 22.1%), as were clinical pregnancy, miscarriage, and ongoing pregnancy rates. There was a significant increase in the proportion of multiple pregnancies in the placebo group (10.3% vs. 36.8%). CONCLUSION(S) Administration of GnRH agonist at the time of implantation does not improve the reproductive outcome of IUI cycles.

Ovarian stimulation length, number of follicles higher than 17 mm and estradiol on the day of human chorionic gonadotropin administration are risk factors for multiple pregnancy in intrauterine insemination

AimThe aim of the present study was to identify the risk factors, their prognostic value on multiple pregnancies (MP) prediction and their thresholds in women undergoing controlled ovarian hyperStimulation (COH) with follicle stimulating hormone (FSH) and intrauterine insemination (IUI).MethodsA case-control study was carried out by identifying in our database all the pregnancies reached by donor and conjugal IUI (DIUI and CIUI, respectively), and compared cycle features, patients’ characteristics and sperm analysis results between women achieving single pregnancy (SP) versus MP. The number of gestational sacs, follicular sizes and estradiol levels on the human chorionic gonadotropin (hCG) administration day, COH length and semen parameters were obtained from each cycle and compared. Student’st-tests for mean comparisons, receiver-operator curve (ROC) analysis to determine the predictive value of each parameter on MP achievement and multiple regression analysis to determine single parameter influence were carried out.ResultsWomen with MP in IUI stimulated cycles reached the adequate size of the dominant follicle (17 mm) significantly earlier than those achieving SP. Also, the mean follicles number, and estradiol levels on the hCG day were higher in the CIUI and DIUI MP group. Nevertheless, only ROC curve analysis revealed good prognostic value for estradiol and follicles higher than 17 mm. Multiple regression analysis confirmed these results. No feature of the basic sperm analysis, either in the ejaculate or in the prepared sample, was different or predictive of MP. When using donor sperm, different thresholds of follicle number, stimulation length and estradiol in the prediction of MP were noted, in comparison with QUI.ConclusionsMP in stimulated IUI cycles are closely associated to stimulation length, number of developed follicles higher than 17 mm on the day of hCG administration and estradiol levels. Also, estradiol has a good predictive value over MP in IUI stimulated cycles. The establishment of clinical thresholds will certainly help in the management of these couples to avoid undesired multiple pregnancies by canceling cycles or converting them intoin vitro fertilization procedures.

P01.28: Analysis of nuchal translucency measurements in pregnancies achieved by assisted reproduction techniques

nasal bone was 13%, combined ultrasound & biochemical detection rate was 91%. 15/17 fetus with trisomy 21 were detected (88.8%) with 9.4% false positive results (4.7% in women younger 35) (cut off 1/250). Conclusion: Combined screening in the first trimester of pregnancy is an efficient approach for detection of fetal chromosomal diseases. Screening in the first trimester is more effective than in the second trimester of pregnancy.