José Navarro

Impact of stage iii–iv endometriosis on recipients of sibling oocytes: matched case-control study

OBJECTIVE To evaluate the impact of severe endometriosis on IVF-ET outcome in women receiving oocytes from the-same donor. DESIGN A matched case-control study. SETTING Oocyte donation program at the Instituto Valenciano de Infertilidad. PATIENT(S) Fifty-eight recipients were included in a matched case-control study of IVF-ET in our oocyte donation program. Twenty-five patients were diagnosed by laparoscopy with stage III-IV endometriosis (group I), while the remaining 33 were free of the disease (group II). On the day of retrieval, oocytes from a single donor were donated to recipients from both groups. Some of the donors supplied oocytes for more than 2 patients. Recipients received steroid replacement therapy for endometrial preparation. INTERVENTION(S) Ovarian stimulation and oocyte retrieval in donors. Uterine embryo transfer (ET) in recipients after appropriate exogenous hormone replacement therapy (HRT). MAIN OUTCOME MEASURE(S) Pregnancy, implantation, miscarriage, and live birth rates. RESULT(S) The number of oocytes donated and fertilized, as well as the number of available and transferred embryos, was not statistically different between the two groups. Pregnancy, implantation, and miscarriage rates were not affected by stage III-IV endometriosis when compared with the control group. The live birth rate was 28.0% in the group with endometriosis and 27.2% in the control group. CONCLUSION(S) These results show that implantation is not affected by stage III-IV endometriosis. Given the contemporary methods of endometrial preparation for transfer of embryos derived from donor oocytes, any potential negative effect of severe endometriosis on the uterine environment is undetectable.

Endometrial quality in infertile women with endometriosis.

Several analyses in our infertility (IVF) and oocyte donation programs were carried out to gain clinical knowledge of the factors involved in the etiology of endometriosis‐associated infertility. We first compared the IVF outcomes in women with tubal infertility and endometriosis. The results indicated that patients with endometriosis had a poorer IVF outcome in terms of reduced pregnancy rate per cycle, per transfer, and reduced implantation rate per embryo replaced. We then evaluated embryo development in vitro in women with and without endometriosis who underwent IVF and embryo replacement 72 hours after oocyte retrieval. We observed that compared to controls, patients with endometriosis had a significantly reduced number of blastomeres per embryo as well as an increased incidence of arrested embryos in vitro. In subsequent studies we compared fertility parameters in patients receiving donor oocytes. We noted that when donor oocytes came from patients without known endometriosis, embryo development and implantation rates were similar in patients with and without endometriosis. However, when the results of oocyte donation were classified according to the nature of the oocytes donated, patients who received embryos derived from oocytes from women with endometriotic ovaries showed a significantly reduced implantation rate compared to the controls. Taken together, these observations suggest that IVF in patients with endometriosis may be related to alterations within the oocyte, which, in turn, result in embryos of lower quality with a reduced ability to implant.

How does endometriosis affect infertility

Prospective and retrospective clinical trials suggest a decreased oocyte and embryo quality in women with endometriosis. Based on these observations, the authors described an altered intrafollicular milieu in endometriosis, which explains the bad quality oocytes and the resulting embryos with lower capacity to implant. Whether these changes affect the oocytes or are the consequence of genomic alterations manifested by biochemical and chromosomal differences in healthy women is an unresolved issue. If the effects of endometriosis on follicular development are nongenomic in origin, modulation of the process of folliculogenesis may be sufficient to treat the disease and cure infertility associated with endometriosis. A genomic defect needs specific genetic therapy, which currently is not available.

Importance of the biospy date in autologous endometrial cocultures for patients with multiple implantation failures

OBJECTIVE To analyze the effectiveness of autologous endometrial coculture by the cycle day of the endometrial biopsy. DESIGN Retrospective study. SETTING University-based IVF center. PATIENT(S) Two hundred eight patients with multiple IVF failures. INTERVENTION(S) Embryos were split and randomly allocated to growth on autologous endometrial coculture or conventional media. MAIN OUTCOME MEASURE(S) Embryo quality and pregnancy outcome. RESULT(S) The overall clinical pregnancy rate was 41.8%. Embryos grown on autologous endometrial coculture were of higher quality (more blastomeres and less fragmentation) than embryos grown with conventional media. Early luteal biopsies (<5 days after LH surge) for autologous endometrial coculture did not demonstrate an improvement in embryo quality as compared to the significant improvement demonstrated with later luteal endometrial biopsies (> or =5 days after LH surge). The date of the biopsy was predictive of pregnancy outcome when using autologous endometrial coculture (44.7% [> or =5 days after LH surge] vs. 18.8% [<5 days after LH surge], P=.012). CONCLUSION(S) We have demonstrated an improvement in embryo quality when using autologous endometrial coculture. The improvement in embryo quality and higher pregnancy rates were limited to biopsies > or =5 days after the LH surge. This suggests that mid/late luteal phase endometrium contains factors that enhanced embryo growth and subsequent implantation.

Embryonic Chromosomal Abnormalities Obtained After Rescue Intracytoplasmic Sperm Injection of 1-Day-Old Unfertilized Oocytes

AbstractPurpose: To study if second day intracytoplasmic sperm injection (ICSI) results in chromosomal abnormalities in the embryos. Methods: Rescue ICSI was performed on 14 metaphase II (MII) oocytes after unsuccessful conventional IVF, four were fertilized. Fluorescent in situ hybridization (FISH) was performed on these four embryos and was informative for three. Results: There were two tetraploid embryos, one mosaic embryo with trisomy 21, tetrasomy 18, and tetrasomy for sex chromosomes in one cell and trisomy 22 in another cell. Conclusions: We discourage the use of second day ICSI due to the observed increase in chromosomal abnormalities in these embryos.

Co-Flare stimulation in the poor responder patient: predictive value of the flare response.

AbstractPurpose: In this study we review our experience with a day 2 start, “Co-Flare” protocol analyzing the flare response as a predictor of outcome in patients with a history of a poor response. Methods: This study was conducted at a university based IVF Center. A total of 564 patient cycles over a 2.5-year time frame in patients that had either elevated FSH levels or a previous poor response to conventional leuprolide acetate down-regulated stimulation were retrospectively analyzed. These patients were treated with our co-flare protocol (1.0 mg of leuprolide acetate administered on day 2 and decreased on day 5 to 0.5 mg; gonadotropins initiated on day 3). We analyzed the initial flare response and the outcome for these patients. Results: A total of 564 patients attempted to initiate an IVF cycle. The patients mean age was 39.4 ± 3.7 years. Of the 450 cycles that started, the outcomes were as follows: 24% (108/450) cancellation, 20.4% (92/450) clinical pregnancy per initiated cycle, and a 14.0% delivery rate per initiated cycle. Patients with an estradiol flare that doubled were less likely to have cycles cancelled (13.6% vs. 35.6%, P < 0.01), but no differences were noted in pregnancy outcome if the cycle was not cancelled once the patient made it to retrieval. Conclusions: We have demonstrated an overall 14.0% delivery rate per initiated cycle in these “poor prognosis” patients. While the initial flare response (as indicated by a doubling of the estradiol by the second day of stimulation) was indicative of a better stimulation, no difference in pregnancy outcome was seen if the patient underwent retrieval.

Autologous endometrial coculture in patients with a previous history of poor quality embryos.

AbstractPurpose: To evaluate the effect of autologous endometrial coculture in patients (less than 36 years old) with a history of a single IVF failed cycle associated with poor quality embryos. Methods:Design: Controlled clinical study. Setting: University-based in vitro fertilization center. Patients: Twenty-six patients with a history of a single prior failed IVF-ET with poor preembryo quality. Intervention(s): Autologous endometrial coculture. Main outcome measures: Preembryo blastomere numbers and cytoplasmic fragmentation rates were compared between the treatment and previous cycle. Clinical pregnancy rates were analyzed. Results: Twenty-six women with an average age of 32.8 ± 2.9 years underwent treatment. On Day 3 the overall mean number of blastomeres per preembryo on coculture compared to conventional medium in a previous cycle was 6.1 ± 1.8 vs. 5.1 ± 1.3 (P = 0.01; Wilcoxon test). The average percentage of cytoplasmic fragments on coculture compared to the conventional medium in a previous cycle was 14% ± 10 vs. 22% ± 13 (P = 0.003; Wilcoxon test). At transfer the mean number of blastomeres per preembryo on coculture was 7.4 ± 1.8 compared to 6.7 ± 1.5 on conventional medium in a previous cycle (P = 0.02; Wilcoxon test). The clinical pregnancy rate (positive fetal cardiac activity) per patient was 88.5%. The delivery rate was 73.1% (19/26). Conclusions: There was an improvement in the preembryo quality for preembryos on autologous endometrial coculture compared to noncocultured preembryos from the same patient in a previous cycle. An excellent delivery rate was subsequently found.

Cytokines in older patients undergoing in vitro fertilization: the relationship to the response to controlled ovarian hyperstimulation.

Purpose:Our purpose was to assess the endocrine, autocrine, and paracrine milieu in follicles of older women undergoing stimulated cycles, comparing normal (NR) and low (LR) responses, based on the measurement of interleukin (IL)-1β, IL-6, and vascular endothelial growth factor (VEGF) in serum and follicular fluid (FF).Methods:A total of 40 women entered the study, divided into three groups: (1) older patients (>37 years) with NR (age-NR; n = 18); (2) older women with LR (age-LR; n = 11); and (3) normal controls, aged <35 years (control; n = 11). IL-1β, IL-6, and VEGF measured in serum (day of ovum pickup) and FF, employing ELISAs.Results:Follicular fluid IL-6 was significantly (P < 0.05) higher in age-LR compared to the other two groups. IL-6 and VEGF showed a 4- to 20-fold increase in FF compared to blood, suggesting the ovary as an additional source of both cytokines. IL-1β levels remained unchanged in FF compared to blood and, also, among groups.Conclusions:These data provide further evidence that the endocrine, paracrine, and/or autocrine status in vivo of older patients is different from that of younger women and suggest that cytokines, specifically IL-6, may be involved in the changes observed during senescence within the ovary.