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Biomedical subjects

J Remohí

Publications and source records attributed to J Remohí.

At least 73 records · Page 4Linked to original sources

Molecular interactions between embryo and uterus in the adhesion phase of human implantation.

Molecular interactions at the embryo-maternal interface at the time of implantation is an exciting field demanding a wide effort in order to understand the crucial process of embryonic implantation. The objective of the present work is to demonstrate the existence of a specific communication pathway (at the molecular level) between embryo and endometrium in the adhesion phase of human embryonic implantation. This pathway of molecular interactions is apparently initiated by the endometrium in the presence of an implanting blastocyst. It is mediated through the embryonic interleukin 0(IL)-1-alpha + IL-1-beta, and the target is the endometrial epithelial beta-3 integrin subunit. If the relevance of beta-3 is accepted as a marker of uterine receptively, these observations may imply that the normal hormonally-regulated human endometrium is the trigger of molecular events preparing the blastocyst to efficiently communicate and regulate endometrial adhesion molecules in order to implant.

Antigens, CD↗

Testicular sperm extraction and intracytoplasmic sperm injection: a chance of fertility in nonobstructive azoospermia.

PURPOSE: We evaluate the efficacy of testicular sperm extraction and results of intracytoplasmic sperm injection in cases of nonobstructive azoospermia. In addition, we define predictive parameters for successful testicular sperm extraction in these patients. MATERIALS AND METHODS: A total of 154 patients with nonobstructive azoospermia underwent multiple testicular biopsies to obtain testicular spermatozoa and for histopathological diagnosis. Results of testicular sperm extraction were related to suspected etiology of azoospermia, patient age, maximal testicular volume, serum follicle-stimulating hormone and histopathology. When testicular sperm extraction was successful, intracytoplasmic sperm injection was performed. RESULTS: Spermatozoa were obtained from 63 patients (41%). No potential predictive parameters precluded successful testicular sperm retrieval. Fertilization was achieved in 74 of 76 intracytoplasmic sperm injection cycles. Normal 2 pronuclear fertilization was observed in 55% of the intact oocytes after microinjection. Clinical pregnancies were achieved in 21 cases for a pregnancy rate of 28% per started cycle. There were 4 miscarriages and 11 live births from 9 deliveries. In addition, a set of twins died after birth because of prematurity. Seven pregnancies were ongoing. CONCLUSIONS: Men with nonobstructive azoospermia may have areas of preserved spermatogenesis in the testicles, and these spermatozoa can be retrieved for intracytoplasmic sperm injection. Although some clinical and histopathological parameters are associated with significantly different sperm recovery rates, it is not possible to predict with certainty the outcome of testicular sperm extraction in an individual patient. If testicular sperm extraction is successful, intracytoplasmic sperm injection offers the chance of pregnancy to these otherwise intractably infertile couples.

Adult↗

Oocyte quality in polycystic ovaries revisited: identification of a particular subgroup of women.

PURPOSE: Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. METHODS: This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n = 4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n = 16) was PCO patients in whom IVF (n = 38) and/or oocyte donation cycles (n = 42) resulted in pregnancies; and group III (n = 13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. RESULTS: There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. CONCLUSIONS: This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.

Adult↗

Pregnancy and birth rates after oocyte donation.

OBJECTIVE: To determine accumulated conception and live birth rates in ovum donation. DESIGN: Retrospective study from a computer database. Pregnancies with one gestational sac observed by ultrasound have been included as conceptional cycles and pregnancies that resulted in one live child were recorded for the analysis of the live birth rates. Life table analysis was applied. SETTING: Oocyte donation program at the Instituto Valenciano de Infertilidad. PATIENT(S): Three hundred ninety-seven recipients undergoing a total of 627 ETs were analyzed. INTERVENTION(S): Ovarian stimulation and ovum pick-up in donors. Uterine ET in recipients after appropriate exogenous steroid replacement. MAIN OUTCOME MEASUREMENT(S): Accumulated and estimated (95% confidence intervals [CI]) conception and live birth rates in the oocyte donation program as well as considering age and cause of infertility of the recipients. RESULT(S): Pregnancy rate after one cycle was 53.4% (CI 50.9% to 55.9%), with a delivery rate of 42.6% (CI 40.1% to 45.1%). Accumulated pregnancy rate increased up to 94.8% (CI 90.6% to 99.0%) after four transfers. Similarly, live birth rates reached 88.7% (CI 88.1% to 89.3%) after four attempts of ET by ovum donation. Cycle fecundity rates were maintained at approximately 50% after each attempt. Implantation rate was 18.3% (430/2,340 replaced embryos). Age and cause of entering the program did not influence the overall results of ovum donation. CONCLUSION(S): Oocyte donation is a successful treatment modality for infertile couples that offers even higher success rates than natural conception. No difference in cumulative pregnancy rate was observed regardless of recipient age, indication for oocyte donation, or number of cycles attempted.

Adult↗

The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination.

OBJECTIVE: To determine an optimal insemination technique in patients undergoing IVF after failed IUI and the role of intracytoplasmic sperm injection (ICSI) in such cases. DESIGN: Prospective, randomized study in couples with unexplained infertility (n = 63) and mild endometriosis (n = 7) undergoing IVF after four IUI cycles. Sibling oocytes were randomized into standard IVF or ICSI insemination according to the order of retrieval. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Italy. PATIENT(S): Seventy couples with unexplained infertility undergoing IVF after failing to conceive with controlled ovarian stimulation and IUI. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, and embryo quality were compared in IVF- and ICSI-inseminated oocytes. RESULT(S): There was no significant difference in fertilization rates between ICSI (60.4%) and conventional IVF (54.0%). Similarly, there was no difference in embryo quality between both groups. There was no total fertilization failure in ICSI-inseminated oocytes, whereas 8 (11.4%) of 70 cases showed absence of fertilization when conventional IVF was used. CONCLUSION(S): Couples with unexplained infertility and mild endometriosis failing to conceive with IUI and undergoing IVF have an 11.4% chance of fertilization failure that can be overcome easily by using ICSI in at least some oocytes. ICSI, however, is not superior to IVF as an insemination technique in most cases. These data should be used in counseling patients.

Adult↗

Effect of disruption versus continuation of gonadotrophin-releasing agonist after human chorionic gonadotrophin administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization.

Previous studies have described the luteolytic effect of gonadotrophin-releasing hormone agonist (GnRHa) administered in the early luteal phase. The present work was undertaken to compare in a prospective and randomized design the effect of disruption versus continuation of daily GnRHa after human chorionic gonadotrophin (HCG) administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization (IVF). Two different studies were designed and a total of 38 ovum donors, aged 23-30 years, were included. In the first study, the effect of GnRHa on the early luteal phase of IVF-stimulated cycles was investigated (n = 27); the patients were divided into two groups, according to whether they stopped (n = 13) or continued with daily GnRHa injections (n = 14) for an additional period of 15 days after HCG administration. Blood was drawn from luteal phase days 2 to 6 (day 0 = day of HCG administration) and oestradiol and progesterone concentrations were analysed. The second study focused on the effects of continuation versus disruption of GnRHa administration in the mid-late luteal phase. A similar design was employed including six patients who stopped GnRH on day 0 and five other women who continued GnRHa for 15 days after HCG administration. In this second study, blood was drawn from days 5 to 11 and oestradiol, progesterone and luteinizing hormone (LH) concentrations were analysed. IVF parameters were similar in both groups. The results indicate that continuous GnRHa administration, after HCG injection, does not produce changes in oestradiol, progesterone and LH concentrations in the early, mid- and late luteal phases compared to those patients in whom GnRHa is discontinued at the day of HCG administration. The present work demonstrates that, when ovulation induction is performed, the corpus luteum is driven primarily by the HCG, regardless of the administration or disruption of GnRHa in the luteal phase. This suggests that the lack of differences between continuation versus disruption of GnRHa may be due to the accumulation of the product over the previous 2-3 weeks of treatment.

Adult↗

Endometrial thickness and serum oestradiol concentrations as predictors of outcome in oocyte donation.

Adequate endometrial preparation with exogenous steroids is mandatory for successful ovum donation. This study was undertaken to assess the value of endometrial thickness by ultrasound and serum oestradiol as predictors of ovum donation outcome and to analyse the correlation between serum oestradiol concentrations and the endometrial thickness. Endometrial thickness and serum oestradiol concentrations on the day of oocyte donation were recorded and compared to several in-vitro fertilization parameters. The cycles (n = 465) were classified according to serum oestradiol values and endometrial thickness. Comparison of the groups showed that endometrial thickness was significantly (P = 0.002) higher when serum oestradiol was >400 pg/ml as compared to <100 pg/ml. Pregnancy and implantation rates did not differ among the groups, women with serum oestradiol <50 pg/ml having similar outcome to the remaining cases. Endometrial thickness showed a similar picture in terms of pregnancy and implantation. Also, women with an endometrium <4 mm in size had normal pregnancy and implantation rates. There was a positive correlation (P = 0.0044) between endometrial thickness and implantation, as well as between endometrial thickness and serum oestradiol (P = 0.0184). None of the parameters examined was able to predict ovum donation outcome. It is concluded that endometrial thickness is preferred to serum oestradiol for the monitoring of endometrial development, although neither is able to predict success in oocyte donation.

Adult↗

The impact of endometriosis in couples undergoing intracytoplasmic sperm injection because of male infertility.

To assess the impact of endometriosis on intracytoplasmic sperm injection (ICSI) outcome, we have retrospectively evaluated 980 ICSI cycles, comparing the results of women with and without endometriosis. A total of 101 cycles was identified in which various degrees of endometriosis were involved, and in the remaining 879 cycles, male infertility was the only cause of infertility. Ejaculated spermatozoa were microinjected in all cycles. There was a significant reduction (P = 0.004) in the number of oocytes retrieved from women with endometriosis as compared to those without endometriosis. However, there were no significant differences in either fertilization or pregnancy and implantation rates between women with or without endometriosis. We conclude that the presence of endometriosis in patients undergoing ICSI because of severe male infertility does not affect fertilization, pregnancy and implantation rates, although significantly fewer oocytes are retrieved from patients with endometriosis.

Adult↗

Accidental exposure to daily long-acting gonadotrophin-releasing hormone analogue administration and pregnancy in an in-vitro fertilization cycle.

A case of successful pregnancy in an in-vitro fertilization cycle, in spite of an accidental exposure to daily long-acting gonadotrophin-releasing hormone analogue administration, is reported. The patient underwent two intracytoplasmic sperm injection cycles with thawed epididymal spermatozoa, in which, due to a pharmacist's mistake, ovarian stimulation was carried out by a combination of long-acting gonadotrophin-releasing hormone agonist (leuprolide depot) and gonadotrophins. A successful singleton pregnancy was achieved after intrauterine embryo transfer with the birth of a healthy boy after 38 weeks. We describe the circumstances and results of this clinical case, as well as reviewing the literature.

Adult↗

Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human endometrial epithelial cells in vitro.

In the present study, we examined the embryonic regulation of beta 3 integrin in human endometrial epithelial cells (EEC) at the protein level and analyzed putative embryonic factors responsible for this regulation. The model employed is based on a clinical in vitro fertilization program in which single human embryos were cocultured with EEC until blastocyst stage and then transferred back to the uterus. After embryo transfer, EEC wells were divided according to the embryonic status reached: EEC with embryos that achieved the blastocyst stage, EEC with arrested embryos, and EEC without embryos. Immunostaining for beta 3 was positive in plasma membrane of EEC. Flow cytometry showed a mean percentage of beta 3-stained cells of 24.1 +/- 5.7 in EEC cocultured with embryos that achieved the blastocyst stage (n = 13) vs. 9.5 +/- 1.6 (P < 0.05) in those EEC cultured with arrested embryos (n = 12). Immunostaining for alpha 1 and alpha 4 integrins was negative in EEC monolayers studied, regardless of the presence or absence of embryos, and these findings were confirmed by flow cytometry. The possibility that the embryonic IL-1 system and leukemia inhibitory factor were involved in the endometrial beta 3 up-regulation was investigated by neutralizing experiments demonstrating a significant inhibition of beta 3-stained cells when EEC monolayers were cultured in the presence of EEC/blastocyst-conditioned media with (n = 4) vs. without (n = 8) antihuman interleukin (IL)-1 alpha + IL-1 beta (1.65% vs. 14.6%; P < 0.05). Dose-response experiments further demonstrated an up-regulation of beta 3 positive cells when IL-1 alpha + IL-1 beta were added to the medium at a concentration of 10 pg/mL compared with control medium without added cytokines (40% vs. 20%, n = 4). The functional relevance of the EEC beta 3 up-regulation was tested using a mouse blastocyst adhesion assay. More mouse blastocysts attached to EEC previously in contact with human blastocyst (72.7%) compared with those EEC previously in contact with arrested embryos (40%). Our results demonstrate the selective effect of a developing human embryo on EEC expression of beta 3, which is maximal when a human blastocyst instead of an arrested embryo is considered. Furthermore, the embryonic IL-1 system seems to be involved in the EEC beta 3 up-regulation, reinforcing the concept of precise paracrine cross-talk between blastocyst and endometrial epithelium during embryonic implantation.

Adult↗

Factors responsible for multiple pregnancies after ovarian stimulation and intrauterine insemination with gonadotropins.

PURPOSE: The present study was undertaken in order to analyze possible factors that could be responsible for multiple pregnancies in normoovulatory women undergoing superovulation with gonadotropins and intrauterine artificial insemination. METHODS: We retrospectively analyzed several clinical parameters in patients that achieved gestation with this treatment. Patients were divided into two groups depending on sperm origin (husband and donor sperm). Furthermore, they were subclassified as follows: (a) cycles resulting in single pregnancies (n = 366), (b) cycles ending in multiple pregnancies (n = 126), and (c) a control group composed of unsuccessful cycles (n = 366). RESULTS: In cycles employing husband's sperm, the age, number of cycles necessary to reach pregnancy, serum estradiol (E2) levels, and number of follicles were significantly (P < 0.05) different in multiple pregnancies compared to single or nonpregnant cycles. In donor insemination, women with multiple pregnancies were significantly younger than nonpregnant patients. There was a significant increase in the number of follicles developed (P < 0.00001) and serum E2 levels on the day of hCG (P < 0.05) in multiple compared to single pregnancies and unsuccessful cycles. The number of motile sperm in the insemination specimen was not different among the established groups. When both types of treatments were grouped, pregnant patients were significantly (P < 0.00001) younger than women with failed cycles. In addition, multifetal pregnancies were significantly (P < 0.05) more frequent in women < 30 years old. E2 production was significantly (P < 0.00008) higher in twin and multifetal pregnancies than in single or nonpregnant cycles. Follicular development was also significantly (P < 0.00001) higher in twin and multifetal pregnancies compared to failed cycles. CONCLUSIONS: The results suggest that young women (< 30 years) who develop more than six follicles with E2 > 1000 pg/ml when stimulated with gonadotropins are at higher risk of multiple gestation. These data may be helpful in preventing this undesired complication of assisted reproduction techniques.

Adult↗

Hormonal regulation of serum and endometrial IL-1 alpha, IL-1 beta and IL-1ra: IL-1 endometrial microenvironment of the human embryo at the apposition phase under physiological and supraphysiological steroid level conditions.

We have investigated serum and intracavitary levels of IL-1 alpha, IL-1 beta and IL-1ra from agonadal women undergoing mock cycles (n = 20) of oocyte donation as a clinical model of controlled hormonal stimulation. Further, we compared the intracavitary IL-1 alpha, IL-1 beta and IL-1ra levels in the microenvironment of the human embryo at the apposition phase, day 5 after progesterone (P) administration using two different clinical models: oocyte donation (n = 20) which provides physiological steroid levels and a higher implantation rate per embryo, and in vitro fertilization (n = 6) with supraphysiological hormonal levels and a lower implantation rate.

Embryonic and Fetal Development↗

Fertilization after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa.

OBJECTIVE: To assess the possibility of cryopreserving testicular tissue extracted sperm for intracytoplasmic sperm injection (ICSI). DESIGN: A report of two cases. Our study was approved by the Ethical Committee at the Instituto Valenciano de Infertilidad. SETTING: In vitro fertilization program at the Instituto Valenciano de Infertilidad. PATIENTS: Two azoospermic patients with severe spermatogenic failure but with focal spermatogenesis on testicular biopsies. In both cases, a first ICSI attempt with fresh testicular biopsy extracted sperm was unsuccessful. INTERVENTIONS: Cryopreservation of testicular spermatozoa in 100-micro L "pills." Intracytoplasmic sperm injection with thawed testicular spermatozoa. MAIN OUTCOME MEASUREMENTS: Fertilization rate, cleavage rate, embryo quality, clinical pregnancy. RESULTS: Fertilization rates were 36 percent and 100 percent after ICSI with fresh testicular spermatozoa, and 63 percent and 57 percent after ICSI with cryopreserved testicular sperm. In both cases, cleavage rates and embryo quality were similar when using fresh and cryopreserved testicular spermatozoa. No clinical pregnancies were achieved. CONCLUSION: High fertilization rates can be obtained after ICSI with frozen-thawed testicular tissue extracted spermatozoa. Cryopreservation of testicular sperm may avoid repetition of testicular biopsies in azoospermic patients in whom the only source of spermatozoa is the testicle.

Adult↗

Lower implantation rates in high responders: evidence for an altered endocrine milieu during the preimplantation period.

OBJECTIVE: To determine serum E2 and P levels around the time of implantation in normal and high IVF responders. SETTING: In Vitro Fertilization program at the Instituto Valenciano de Infertilidad. PATIENTS: Twenty-nine women undergoing IVF, who accepted to be studied daily, were classified according to the number of oocytes retrieved in normal (n = 16) and high responders (n = 13). DESIGN: Prospective study in which blood was drawn daily from the day of hCG administration (day 0) up to 7 days later (day 6). MAIN OUTCOME MEASUREMENTS: In vitro fertilization parameters (number of ampules, FSH-hMG, number of oocytes, fertilization rates, number of transferred embryos, implantation rates, and pregnancy rates); serum E2 and P levels during the 7 days of the study. RESULTS: Implantation rate was significantly higher in normal (18.5%) as compared with high (0%) responders. Estradiol and P levels were elevated significantly in high responders. The E2:P ratio was significantly different between normal and high responders during the preimplantation period. Pregnancy and implantation rates decreased as serum E2 levels increased on days 4 to 6 of the study. CONCLUSIONS: A different endocrine milieu between normal and high responders is detected by daily steroid measurements up to the preimplantation period, suggesting that this difference could be responsible for an impaired implantation in high responder patients undergoing IVF. An increase in serum E2 levels seems to be the cause of this difference.

Chorionic Gonadotropin↗

Effect of age on sperm fertility potential: oocyte donation as a model.

OBJECTIVE: To determine the effect of age on sperm fecundability using oocyte donation as an in vivo model. SETTING: Oocyte donation and IVF programs at the Instituto Valenciano de Infertilidad. DESIGN: Retrospective study in which four groups of oocyte donation cycles were established according to age of the male providing the semen sample: group 1 (n = 31) < 30 years; group 2 (n = 195) 31 to 40 years; group 3 (n = 98) 41 to 50 years; group 4 (n = 21) > 51 years, the oldest being 64 years. All donated oocytes were obtained from patients < 35 years old. MAIN OUTCOME MEASUREMENTS: Male age, sperm characteristics (volume, concentration, motility, morphology), fertilization, embryo quality, pregnancy, implantation, and abortion rates among recipients. RESULTS: Similar sperm characteristics in fresh as well as after preparation for IVF were observed among males of different ages. Fertilization, embryo quality, pregnancy, and implantation were similar among the established groups. The mean age of the females included in each group significantly increased from group 1 to group 4. CONCLUSIONS: Age (up to 64 years) does not affect sperm characteristics or its ability to fertilize human eggs. Similarly, embryo development in vitro as well as implantation in recipient uteri are not affected by age of the male providing the semen sample.

Abortion, Spontaneous↗

Age does not affect uterine resistance to vascular flow in patients undergoing oocyte donation.

OBJECTIVE: To determine whether uterine vasculature is affected by age using oocyte donation as an in vivo model. DESIGN: Prospective longitudinal study in which recipients were grouped according to age. They underwent a successful oocyte donation cycle, and single pregnancies were followed during the first trimester by color Doppler ultrasound in uterine arteries. SETTING: Oocyte donation and IVF program at the Instituto Valenciano de Infertilidad. INTERVENTIONS: Serum E2, P, and hCG levels in single ovum donation pregnancies; pulsatility and resistance indexes in uterine arteries during initial pregnancy. RESULTS: Similar serum levels of E2, P, and hCG in both groups of patients were observed. There was no difference between groups regarding the flow indexes analyzed. CONCLUSIONS: The increased incidence of early pregnancy losses observed in patients > 40 years cannot be attributed to defective response of uterine vasculature to exogenous hormone replacement. Thus, uterine aging does not appear to be a factor influencing the poor reproductive performance of women with advancing age.

Adult↗

Cytokines-adhesion molecules-invasive proteinases. The missing paracrine/autocrine link in embryonic implantation?

How implantation is regulated and brought about remains an enigma. The objective of the present review is to propose a hypothetical model based on our actual knowledge of the role of cytokines, adhesion molecules and invasive proteinases in the adhesion and invasion phases of embryonic implantation. For the purpose of clarity we will describe first what is known about the presence of these molecules in the endometrium and embryo in animal models and their relevance in embryonic implantation. Secondly, since human implantation is unique the presence of these factors in the human endometrium and embryo and their possible clinical relevance is considered separately. Finally, the link between cytokines, adhesion molecules and invasive proteinases as well as their endocrine/paracrine/autocrine regulation is put forward as a possible model that could lead us to a better understanding of the implantation process in humans.

Animals↗