Ernesto Bosch - Academia.edu (original) (raw)
Papers by Ernesto Bosch
Fertility and Sterility, 2010
Objective: To assess whether GnRH agonist administration in the luteal phase improves pregnancy o... more 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 ¼ 172) 8 days after hCG administration, or solvent only (group B; n ¼ 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. (Fertil Steril Ò 2010;94:1065-71.
Fertility and Sterility, 2015
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;-: ---. Ó2015 by American Society for Reproductive Medicine.) Key Words: Antim€ ullerian hormone, antral follicle count, ovarian follicle, ovarian reserve, reproductive life span Discuss: You can discuss this article with its authors and with other ASRM members at
Annals of the New York Academy of Sciences
Several analyses in our infertility (IVF) and oocyte donation programs were carried out to gain c... more 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.
Fertility and Sterility, 2015
To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assiste... more To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors. Retrospective analysis of results obtained from 2,570 analyses. Reproductive genetic laboratory. The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes. None. Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing. Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded. We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 Mendelian diseases in the offspring of patients undergoing ART.
Clinical Endocrinology, 2015
Objective To study the association between serum anti-M€ ullerian hormone (AMH) levels and follic... more Objective To study the association between serum anti-M€ ullerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5Á2-12Á1 lg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. Design Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5Á0-14Á9 pmol/l; higher stratum: 15Á0-44Á9 pmol/l). Patients Infertile women of good prognosis (n = 265). Measurements Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. Results Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P < 0Á001) positive dose responses were observed for the number of follicles ≥12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. Conclusions Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS.
Fertility and Sterility, 2015
Human reproduction update
Sir, We have read the article published in your journal by with much interest. In this review the... more Sir, We have read the article published in your journal by with much interest. In this review the authors properly summarize the mechanisms, origins and incidence of chromosomal mosaicism in humans.
Fertility and Sterility, 2015
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;-: ---. Ó2015 by American Society for Reproductive Medicine.) Key Words: Antim€ ullerian hormone, antral follicle count, ovarian follicle, ovarian reserve, reproductive life span Discuss: You can discuss this article with its authors and with other ASRM members at
Human reproduction (Oxford, England), 2014
Reproductive BioMedicine Online, 2007
The current study evaluated how a sudden fall in serum oestradiol during ovarian stimulation in d... more The current study evaluated how a sudden fall in serum oestradiol during ovarian stimulation in donors affects recipient outcome. After the assessment of pregnancy rate in cases of oestradiol falls of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10% (57.0 versus 45.6%), &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 20% (55.2 versus 44.9%), &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =25% (57.2 versus 41.2%), and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 30 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =30% (57.1 versus 32.0%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), a significantly lower pregnancy rate was observed when the fall was…
PharmacoEconomics Spanish Research Articles, 2005
ABSTRACT
Reproductive Biology and Endocrinology, 2014
The potentially detrimental role of progesterone during the follicular phase has been a matter of... more The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response.
Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomip... more Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels Papanikolaou et al. Reproductive Biology and Endocrinology 2011, 9:85
Fertility and Sterility, 2014
To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) wi... more To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. Seven infertility centers in four countries. Two hundred sixty-five women aged ≤37 years. Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. Number of oocytes retrieved. The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. NCT01426386.
Reproductive BioMedicine Online, 2011
The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ... more The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ovarian reserve remain important clinical and basic science research issues of IVF treatment. Recommending commencement of ovarian stimulation using any of the available exogenous compounds without knowledge of individual ovarian potentials is simplistic and dangerous because of the possible adverse consequences for the woman. The identification of groups of patients likely to benefit from one protocol than another is central to the workup process of IVF. Determining the agents for ovarian stimulation as well as the combination of them, the daily dose and duration according to some background information should be seen as the way to enhance safety and cost-effectiveness. This discussion paper aims to introduce the concept of individualized ovarian stimulation in routine clinical practice and to generate interest for tailored stimulation protocols. RBMOnline
The Journal of Clinical Endocrinology & Metabolism, 2012
Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in... more Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in vitro fertilization (IVF) treatments. The real incidence in natural cycles has been poorly studied, so whether this frequency may be induced by external factors, such as use of gonadotropins for ovarian stimulation, remains unknown.
The Journal of Clinical Endocrinology & Metabolism, 2005
The impact of advancing age on uterine receptiveness has always been a concern of the medical est... more The impact of advancing age on uterine receptiveness has always been a concern of the medical establishment. Oocyte donation (OD) is the perfect model for ascertaining the extent of this relationship, but the literature is somewhat unreliable, mainly due to the limited samples on which the studies are based and insufficient control of important variables such as embryo quality. The present work was developed in a private infertility clinic. We retrospectively evaluate the results of 3089 OD cycles that ended up in a d 3 embryo transfer. Severe male factor infertility was an exclusion criterion. The impact of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age on pregnancy, implantation, and miscarriage rates and obstetric outcome is analyzed, as is the relevance of endometrial thickness, serum estradiol levels, and duration of exogenous estrogen therapy to said rates. Pregnancy and implantation rates are significantly reduced and miscarriage rate is significantly increased from 45 yr of age onward. Concerning obstetric outcome, incidences of hypertension, proteinuria, premature rupture of membranes, second- and third-trimester hemorrhage, and preterm delivery are higher and mean birth weight is lower in this age group. With regard to endometrial preparation, estrogen therapy lasting more than 7 wk is associated with reduced PR and IR (P = 0.01 and P = 0.02, respectively). The results of OD cycles and obstetric outcome are significantly worse when recipients are 45 yr of age or older. Concerning endometrial preparation, results are significantly worse when estrogen therapy lasts more than 7 wk.
Fertility and Sterility, 2010
Objective: To assess whether GnRH agonist administration in the luteal phase improves pregnancy o... more 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 ¼ 172) 8 days after hCG administration, or solvent only (group B; n ¼ 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. (Fertil Steril Ò 2010;94:1065-71.
Fertility and Sterility, 2015
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;-: ---. Ó2015 by American Society for Reproductive Medicine.) Key Words: Antim€ ullerian hormone, antral follicle count, ovarian follicle, ovarian reserve, reproductive life span Discuss: You can discuss this article with its authors and with other ASRM members at
Annals of the New York Academy of Sciences
Several analyses in our infertility (IVF) and oocyte donation programs were carried out to gain c... more 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.
Fertility and Sterility, 2015
To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assiste... more To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors. Retrospective analysis of results obtained from 2,570 analyses. Reproductive genetic laboratory. The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes. None. Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing. Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded. We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 Mendelian diseases in the offspring of patients undergoing ART.
Clinical Endocrinology, 2015
Objective To study the association between serum anti-M€ ullerian hormone (AMH) levels and follic... more Objective To study the association between serum anti-M€ ullerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5Á2-12Á1 lg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a GnRH antagonist protocol. Design Secondary analysis of a randomized controlled trial with stratified randomization according to AMH (lower stratum: 5Á0-14Á9 pmol/l; higher stratum: 15Á0-44Á9 pmol/l). Patients Infertile women of good prognosis (n = 265). Measurements Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. Results Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P < 0Á001) positive dose responses were observed for the number of follicles ≥12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. Conclusions Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels at start of COS.
Fertility and Sterility, 2015
Human reproduction update
Sir, We have read the article published in your journal by with much interest. In this review the... more Sir, We have read the article published in your journal by with much interest. In this review the authors properly summarize the mechanisms, origins and incidence of chromosomal mosaicism in humans.
Fertility and Sterility, 2015
Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche ... more Objective: To evaluate a new fully automated assay measuring antim€ ullerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. Design: Prospective cohort study. Setting: Hospital infertility clinics and academic centers. Patient(s): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. Intervention(s): None. Main Outcome Measure(s): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. Result(s): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho À0.50 for AFC and À0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. Conclusion(s): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool. (Fertil Steril Ò 2015;-: ---. Ó2015 by American Society for Reproductive Medicine.) Key Words: Antim€ ullerian hormone, antral follicle count, ovarian follicle, ovarian reserve, reproductive life span Discuss: You can discuss this article with its authors and with other ASRM members at
Human reproduction (Oxford, England), 2014
Reproductive BioMedicine Online, 2007
The current study evaluated how a sudden fall in serum oestradiol during ovarian stimulation in d... more The current study evaluated how a sudden fall in serum oestradiol during ovarian stimulation in donors affects recipient outcome. After the assessment of pregnancy rate in cases of oestradiol falls of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =10% (57.0 versus 45.6%), &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or = 20% (55.2 versus 44.9%), &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =25% (57.2 versus 41.2%), and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 30 or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =30% (57.1 versus 32.0%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), a significantly lower pregnancy rate was observed when the fall was…
PharmacoEconomics Spanish Research Articles, 2005
ABSTRACT
Reproductive Biology and Endocrinology, 2014
The potentially detrimental role of progesterone during the follicular phase has been a matter of... more The potentially detrimental role of progesterone during the follicular phase has been a matter of controversy for several years; however, few studies have analyzed the effects of combined raised estradiol and progesterone levels on pregnancy outcomes. The aim of the present study was to determine the influence of high progesterone levels on clinical outcomes in the context of high ovarian response.
Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomip... more Aromatase inhibitors have been introduced as a new treatment modality that could challenge clomiphene citrate as an ovulation induction regiment in patients with PCOS. Although several randomized trials have been conducted regarding their use as ovulation induction agents, only few trials are available regarding their efficacy in IVF stimulated cycles. Current available evidence support that letrozole may have a promising role in stimulated IVF cycles, either when administered during the follicular phase for ovarian stimulation. Especially for women with poor ovarian response, letrozole appears to have the potential to increase clinical pregnancy rates when combined with gonadotropins, whereas at the same time reduces the total gonadotropin dose required for ovarian stimulation. However, given that in all of the trials letrozole has been administered in GnRH antagonist cycles, it is intriguing to test in the future how it may perform when used in GnRH agonist cycles. Finally administration of letrozole during luteal phase in IVF cycles offers another treatment modality for patients at high risk for OHSS taking into account that it drastically reduces estradiol levels Papanikolaou et al. Reproductive Biology and Endocrinology 2011, 9:85
Fertility and Sterility, 2014
To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) wi... more To evaluate the dose-response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. Seven infertility centers in four countries. Two hundred sixty-five women aged ≤37 years. Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. Number of oocytes retrieved. The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. NCT01426386.
Reproductive BioMedicine Online, 2011
The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ... more The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ovarian reserve remain important clinical and basic science research issues of IVF treatment. Recommending commencement of ovarian stimulation using any of the available exogenous compounds without knowledge of individual ovarian potentials is simplistic and dangerous because of the possible adverse consequences for the woman. The identification of groups of patients likely to benefit from one protocol than another is central to the workup process of IVF. Determining the agents for ovarian stimulation as well as the combination of them, the daily dose and duration according to some background information should be seen as the way to enhance safety and cost-effectiveness. This discussion paper aims to introduce the concept of individualized ovarian stimulation in routine clinical practice and to generate interest for tailored stimulation protocols. RBMOnline
The Journal of Clinical Endocrinology & Metabolism, 2012
Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in... more Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in vitro fertilization (IVF) treatments. The real incidence in natural cycles has been poorly studied, so whether this frequency may be induced by external factors, such as use of gonadotropins for ovarian stimulation, remains unknown.
The Journal of Clinical Endocrinology & Metabolism, 2005
The impact of advancing age on uterine receptiveness has always been a concern of the medical est... more The impact of advancing age on uterine receptiveness has always been a concern of the medical establishment. Oocyte donation (OD) is the perfect model for ascertaining the extent of this relationship, but the literature is somewhat unreliable, mainly due to the limited samples on which the studies are based and insufficient control of important variables such as embryo quality. The present work was developed in a private infertility clinic. We retrospectively evaluate the results of 3089 OD cycles that ended up in a d 3 embryo transfer. Severe male factor infertility was an exclusion criterion. The impact of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age on pregnancy, implantation, and miscarriage rates and obstetric outcome is analyzed, as is the relevance of endometrial thickness, serum estradiol levels, and duration of exogenous estrogen therapy to said rates. Pregnancy and implantation rates are significantly reduced and miscarriage rate is significantly increased from 45 yr of age onward. Concerning obstetric outcome, incidences of hypertension, proteinuria, premature rupture of membranes, second- and third-trimester hemorrhage, and preterm delivery are higher and mean birth weight is lower in this age group. With regard to endometrial preparation, estrogen therapy lasting more than 7 wk is associated with reduced PR and IR (P = 0.01 and P = 0.02, respectively). The results of OD cycles and obstetric outcome are significantly worse when recipients are 45 yr of age or older. Concerning endometrial preparation, results are significantly worse when estrogen therapy lasts more than 7 wk.