Biomedical subjects
Publications and source records attributed to Raoul Orvieto.
Orthodox Jewish women with a prolonged menstrual flow or short follicular phase may be unable to attend the ritual bath early enough in their cycle for conception to take place. Oral estrogen supplementation may effectively delay ovulation beyond the time of the ritual bath, when intimate relations are allowed, thereby restoring the normal (23%) fecundity rate.
In a study of the possible inter-relationship among müllerian anomalies, hearing loss, and connexin 26 mutations, we evaluated all women in whom müllerian anomalies were diagnosed on hysterosalpingography during a 6-year period (n = 24/519). Audiometric testing revealed five (22.7%) with unrecognized sensorineural hearing loss; however, on genetic evaluation, none harbored a connexin 26 mutation.
Anti-müllerian hormone (AMH) appears to regulate follicular growth. The aim of this study was to investigate AMH serum levels in patients affected by secondary amenorrhea. The AMH was significantly lower (or undetectable) in patients with premature ovarian failure (POF) and significantly higher in patients affected by polycystic ovary syndrome (PCOS). We suggest that serum AMH evaluation could be associated with that of established hormones, such as FSH, LH, and E2, when the activity of hypothalamo-pituitary-ovarian axis is investigated.
The study retrospectively evaluated the influence of triggering final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist on the outcome of IVF cycles. Four hundred and sixty consecutive women admitted to the IVF unit during a 4-year period were enrolled in the study. Ovarian stimulation characteristics and clinical pregnancy rate were compared between three groups: patients at risk of developing ovarian hyperstimulation syndrome (OHSS), undergoing either the long GnRH-agonist protocol (agonist group) or the flexible multidose GnRH-antagonist protocol who received GnRH-agonist for final oocyte maturation (antagonist-agonist group); and patients not at risk of developing severe OHSS undergoing the flexible multidose GnRH-antagonist protocol who received human chorionic gonadotrophin (HCG) for final oocyte maturation (antagonist-HCG group). Implantation and clinical pregnancy rates were lowest in the antagonist-agonist group despite the fact that no difference were was observed in fertilization rates between the groups. Moreover, the high-responder antagonist-agonist group required shorter stimulation and had higher numbers of oocytes retrieved as compared with the high-responder agonist-group. No case of severe OHSS was observed in the antagonist-agonist group. The use of flexible multidose GnRH-antagonist protocol with GnRH-agonist for final oocyte maturation, in high-responder patients, eliminates the risk of OHSS but results in decreased implantation and pregnancy rates.
OBJECTIVE: To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. PATIENTS AND METHODS: All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. RESULTS: Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas. CONCLUSIONS: Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.
AIM: Hysterolaparoscopy is the gold-standard procedure for mechanical evaluation of the female pelvic organs. However, it is invasive and potentially life-threatening. The purpose of the present study was to assess the value of an alternative, minimally invasive technique. METHOD: All consenting women who reached the stage of mechanical evaluation in their infertility work-up were invited to participate in the study. All underwent diagnostic hysteroscopy followed by hysterosalpingo contrast sonography (HyCoSy) performed in a single session on an outpatient basis. Patient clinical data were collected prospectively. RESULTS: Twenty women participated in the study, 6 with primary infertility and 14 with secondary infertility. All procedures yielded satisfactory evaluation of the uterine cavity and uterine and ovarian structures, fallopian tube patency, and relationship between the fallopian tube fimbrial edges and the ovaries. All patients were discharged within 2 h; there were no complications during or after the procedure. CONCLUSION: The combination of hysteroscopy and hysterosalpingo contrast sonography (HyCoSy) can provide a comprehensive, functional and relatively non-invasive evaluation of the female pelvic organs.
BACKGROUND: To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation. DESIGN: Prospective, observational study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENTS: Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation. METHODS: Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups. RESULTS: No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%). CONCLUSION: Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.
OBJECTIVE: A prospective comparative study was conducted to investigate the effect of multifetal pregnancies on the quality of nuchal translucency measurements using an image scoring method. METHODS: The study sample included 72 consecutive multiple gestations (164 fetuses) and 195 singleton gestations (control) matched for maternal age and fetal crown-rump length. Nuchal translucency ultrasound was performed similarly in singleton and multiple pregnancies. A single sonographer scored an elected ultrasound image of each fetus according to a nuchal translucency image scoring method and the mean image score was compared between the whole singleton and multiple gestation groups and between subgroups defined by fetal distance from the abdominal wall. RESULTS: There was no significant difference in mean image score between the multiple and singleton gestation groups (6.60 +/- 1.3 and 6.69 +/- 1.5, respectively; p = 0.595). Within the multiple gestation group, there was a significant difference in mean score between fetuses positioned proximal to the abdominal wall (n = 72) (3.7 +/- 1.1) and both the middle fetuses (6.2 +/- 1.4; p < 0.01) and distal fetuses (5.7 +/- 1.06; p < 0.008). There was no difference between the proximal fetuses and controls. CONCLUSIONS: The fetuses in multiple pregnancies that are located further from the abdominal wall have a poorer image score.
OBJECTIVE: Soluble CD40 ligand is a transmembrane protein shed from activated platelets that is involved in the activation of endothelial cells. Findings that estradiol (E2) has an inhibitory effect on inflammation and platelet function and that serum E2 levels are low in women with preeclampsia prompted us to investigate the association between soluble CD40 ligand and serum E2 levels in normal pregnancy and in preeclampsia. METHODS: A case-control single-center design was used. The sample included 22 women with severe preeclampsia, 22 matched normotensive pregnant women, and 22 nonpregnant women. Enzyme immunoassay was used to measure soluble CD40 ligand. RESULTS: Significantly higher levels of soluble CD40 ligand were detected in the nonpregnant women (23,767 +/- 15,637 pg/mL) and in the women with preeclampsia (21,025 +/- 45,386 pg/mL) than in the normotensive pregnant women (8,292 +/- 5,926 pg/mL) (P = .026). No significant correlation between soluble CD40 ligand levels and E2 levels was observed. CONCLUSION: The higher levels of soluble CD40 ligand detected in women with preeclampsia may indicate an exaggerated activation of platelets and endothelial cells. LEVEL OF EVIDENCE: II-2.
AIM: To investigate the behavior and association of serum sex-steroids and serum CD40 ligand in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Prospective, observational study. SETTING: The IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 patients undergoing the long gonadotropin-releasing hormone-analog protocol: (i) day on which adequate suppression was obtained (Day-S); (ii) day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (iii) day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CD40 ligand were compared among the three time points. RESULTS: During gonadotropin treatment, serum ovarian sex steroids (estradiol, progesterone, free testosterone and androstenedione) significantly increased while CD40 ligand levels nonsignificantly decreased. After hCG administration, there was a significant increase in the levels of serum CD40 ligand, ovarian androgens, and progesterone, with a significant decrease in estradiol levels. No correlations were observed between CD40 ligand and ovarian sex-steroid levels or other treatment variables. CONCLUSION: The administration of hCG leads to activation of systemic inflammation, as reflected by CD40 ligand levels. This, in turn, may lead to the development of ovarian hyperstimulation syndrome via several mechanisms, including an increase in several angiogenic factors.
AIMS: To investigate the association between method of contraception and time to conception in a normal community-based population. DESIGN: Prospective, cross-sectional, survey. SETTING: Large comprehensive ambulatory women's health center. PATIENTS AND METHODS: One thousand pregnant women at their first prenatal obstetrics visit were asked to complete a self-report questionnaire. The return to fertility was analyzed by type of contraceptive method, duration of use, and other sociodemographic variables. RESULTS: Response rate was 80% (n=798). Mean age of the patients was 29.9+/-5 years. Seventy-five percent had used a contraceptive before trying to conceive: 80% oral contraceptives, 8% intrauterine device, and 7% barrier methods. Eighty-six percent conceived spontaneously. Contraceptive users had a significantly higher conception rate than nonusers in the first 3 months from their first attempt at pregnancy. Type of contraception was significantly correlated with time to conception. Pregnancy rates within 6 months of the first attempt was 60% for oral contraceptive users compared to 70 and 81% for the intrauterine device and barrier method groups, respectively. There was no correlation between time to conception and parity or duration of contraceptive use. Other factors found to be significantly related to time to conception were older age of both partners and higher body mass index. CONCLUSIONS: Contraception use before a planned pregnancy does not appear to affect ease of conception. Type of method used, although not duration of use, may influence the time required to conceive.
OBJECTIVE: The objectives of this study were: (1) to determine anti-Mullerian hormone (AMH) levels in menopausal women, and (2) to confirm the source of AMH in cycling women and its disappearance after the removal of the source. METHODS: An observational and prospective study was conducted. RESULTS: A total of 47 women were recruited for the study. The study population consisted of the following groups of patients: (A) women of late reproductive age (n = 24; mean age +/- SD, 44 +/- 2.8 years); (B) menopausal women (n =14; mean age, 56 +/- 4 years); and (C) regularly cycling women undergoing surgical menopause (n = 9; mean age, 43 +/- 4 years). Blood samples were obtained from all patients. In patients undergoing surgery, blood samples were obtained before and after surgery. AMH was undetectable in 13 of 14 postmenopausal women, whereas it was undetectable in only two of 24 women of late reproductive age. A significant negative correlation has been found between AMH and age or follicle-stimulating hormone (FSH) in women of late reproductive age. In women who were candidates for oophorectomy, samples were obtained 3-5 days after surgery. AMH was undetectable after the surgery in all women. CONCLUSIONS: We found that AMH levels decreased in women in the late reproductive period and that menopause and ovariectomy in regularly cycling women are associated to undetectable AMH in serum. These observations confirm that the ovary could be the only source of AMH in women and that it is a novel marker for ovarian aging.
OBJECTIVE: Insulin autoantibodies (INSAAbs) are associated with the onset and progression of type 1 diabetes. Their presence in siblings of patients with type 1 diabetes precedes the development of overt diabetes. The precise time of INSAAbs onset and their relationship to diabetes triggering factors remains unknown. We sought to determine the prevalence and nature of INSAAbs in neonates with and without a sibling affected by type 1 diabetes. METHODS: One hundred and twenty four healthy non-diabetic neonates were studied; 12 had a sibling with type 1 diabetes and 112 had no first-degree relatives with the disease. Cord blood samples were collected from the neonates and their mothers at birth and again from the neonates whose initial sample was INSAAbs-positive at 3 months of age. INSAAbs titer was tested using a competitive radiobinding assay. To further characterize the nature of this binding capacity, the assay was repeated twice, before and after incubation with protein A or insulin-like growth factor (IGF-1). RESULTS: Specific insulin-binding activity was noted at birth in 8/12 neonates with a diabetic sibling (66%) and in 79/112 (70%) control newborns. None of the maternal samples from either group were INSAAb-positive. By age 3 months, INSAAb levels had normalized in 90% of the neonates in both groups. Protein A did not induce precipitation of bound insulin complexes, and IGF-1 failed to displace bound insulin from the cord blood. CONCLUSIONS: Although more than 70% of cord blood samples specifically bound insulin, this action is probably unrelated to the passive transfer of IgG antibodies during pregnancy or to cross-reactivity with the IGF-binding proteins. Furthermore, INSAAb cannot be a predictive sign for early development of type 1 diabetes in the first 3 months of age.
OBJECTIVE: To assess whether bed rest following the embryo transfer (ET) procedure contributes to the implantation process and pregnancy rate. DESIGN: A prospective (patient-influenced) study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENT(S): Four hundred six patients undergoing controlled ovarian hyperstimulation and IVF. INTERVENTION(S): All women undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles in our unit were given a special individual counseling session before the ET procedure in which they were informed that our previous experience showed no advantage for bed rest over immediate ambulation after ET. The women were allowed to select the practice of their choice, and they were assured that their decision would have no influence on their further treatment. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcome were compared between the two groups (bed rest and immediate ambulation). RESULT(S): Of the 406 patients counseled during the study period, 167 preferred immediate ambulation and 239 opted to stay in the unit for 1 hour's bed rest. There were no significant differences between the groups in mean patient age, number of embryos transferred, and other variables of the assisted reproductive technique cycles. Pregnancy rates did not differ between the groups: 41 out of 167 (24.55%) in the immediate-ambulation group and 51 out of 239 (21.34%) in the bed-rest group. CONCLUSION(S): Immediate ambulation following the ET procedure has no adverse influence on the ability to conceive.
This study investigated the effect of intravaginal administration of probiotics immediately after oocyte retrieval on vaginal colonization and outcome of the IVF-embryo transfer cycle. One hundred and seventeen women who underwent ovarian stimulation and IVF were randomized immediately after oocyte retrieval into two groups: those who received intravaginal probiotics (study group, n = 50) and those who did not (control group, n = 67). Vaginal colonization with lactobacilli and pregnancy rate were compared between the two groups. No significant between-group differences were observed in patient age, oestrogen and progesterone concentrations on day of human chorionic gonadotrophin administration, number of oocytes retrieved, fertilization rate, number of embryos transferred, or pregnancy rate. The presence of lactobacilli in the vagina during oocyte retrieval or embryo transfer did not improve the pregnancy rate. Furthermore, intravaginal administration of lactobacilli following oocyte retrieval did not affect the prevalence of lactobacilli during embryo transfer, or the pregnancy rate. Intravaginal probiotic supplementation immediately after oocyte retrieval has no effect on vaginal colonization or pregnancy rate in IVF cycles.
OBJECTIVE: To determine the levels of serum P-selectin in patients undergoing controlled ovarian hyperstimulation (COH) cycles with urinary (uGn) versus recombinant gonadotropins (rGn) and their possible correlation with COH variables. METHODS: This study was carried out in a large university-based infertility and in vitro fertilization unit. A total of 14 consecutive patients underwent our routine COH protocol for unexplained infertility with either uGn or rGn. Blood was drawn three times during the COH cycle: on day 2 or 3 of the menstrual cycle and before gonadotropin treatment (day-0); on the day of or prior to human chorionic gonadotropin (hCG) administration (day-hCG); and on the day of ovulation (day-OVU). Levels of sex steroids and serum P-selectin were compared among the three time points between the uGn and rGn subgroups. P-selectin was measured with a commercial quantitative sandwich immunoassay technique. RESULTS: In both Gn subgroups, there was a non-significant increase in P-selectin level between day-hCG and day-0. In the rGN subgroup, no significant difference was observed in P-selectin levels between day-OVU and day-hCG. In the uGn subgroup, P-selectin levels were significantly lower in day-OVU as compared to day-hCG (p < 0.04) and day-0 (p < 0.04). No differences were noted between the uGn and rGn subgroups in patient age, number of gonadotropin ampules used or estradiol and progesterone levels during the COH cycle or P-selectin on day-0 or day-hCG. However, on day-OVU, P-selectin levels were significantly lower in the uGn than the rGn subroups (p < 0.01). CONCLUSION: The increase in serum P-selectin level during COH until the peak of estradiol level was significantly attenuated after hCG administration in patients pretreated with uGn, but not rGN. It would therefore be prudent in patients at risk of developing thromboembolism undergoing COH to use uGN rather than rGN in order to attenuate platelet activation.
AIM: To investigate the behavior and association of serum androgen and serum C-reactive protein (CRP) in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Prospective, observational study.Setting. An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 15 patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CRP were compared among the three time points. RESULTS: There was a significant increase in serum ovarian androgen levels during gonadotropin treatment. After hCG administration, there was a significant increase in the levels of both serum CRP and ovarian androgens (testosterone, androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone). Significant correlations were observed between CRP and ovarian androgen levels but not with dehydroepiandrosterone sulfate or estradiol levels. CONCLUSION: In patients undergoing COH for IVF, ovarian androgen levels increase in correlation with the degree of inflammation, as reflected by CRP levels. Further studies are necessary to elucidate whether androgens play a role in or are predictive of the systemic inflammatory response in COH.
AIM: To investigate androgen behavior during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: A prospective, observational study. SETTING: An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 consecutive patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). RESULTS: There was a significant increase in serum sex steroid levels during gonadotropin treatment. After hCG administration, there was a significant increase in levels of serum 17-hydroxyprogesterone (17-OHP) and ovarian androgens (total and free testosterone and androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone sulfate). Significant correlations were observed between plasma estradiol (E(2)) and androgen levels during COH and until hCG administration, but not after hCG administration. The E(2)/testosterone ratio increased significantly during COH and until hCG administration, and then decreased significantly. The number of oocytes retrieved correlated significantly with serum 17-OHP, E(2) and E(2)/testosterone ratio. The number of gonadotropin ampoules used correlated inversely only with serum E(2) levels. CONCLUSION: In patients undergoing COH for IVF, androgen levels increase in response to gonadotropin, and then again after hCG administration. Although the E(2)/testosterone ratio correlates with the number of oocytes retrieved, androgen levels do not.