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Objective To investigate the effect of two laparoscopic techniques for treatment of ovarian endometriomas on recurrence rate. Design Prospective randomized clinical trial. Setting University teaching hospital. Patient(s) Ninety women with ovarian endometriomas. Intervention(s) Patients were randomly selected to undergo either laparoscopic cystectomy (group 1) or laser vaporization (group 2) of ovarian endometrioma. Main Outcome Measure(s) Recurrence, evaluated by ultrasound scan examination, was assessed at 12 and 60 months of follow-up. Result(s) Endometrioma recurrence rate was higher, though not significantly different, in group 2 at 60 months of follow-up. Nevertheless, at 12 months of follow-up recurrences were statistically higher in group 2. Conclusion(s) The comparison between laparoscopic laser ablation and laparoscopic cystectomy for ovarian endometriomas after long-term follow-up showed earlier recurrences and a higher recurrence rate in the laser group, although at 5 years of follow-up there were no statistically significant differences.

Objective To assess the effect of surgeon's increasing experience in conservative laparoscopic surgery of women with rectovaginal endometriosis on the surgical outcome of these patients recurrence rate. Design Prospective cohort study. Setting University teaching hospital. Patient(s) The first 60 consecutive patients undergoing laparoscopic conservative surgery for symptomatic rectovaginal endometriosis at our institution during a 4- year period. Intervention(s) Cases were classified into two groups according to the date of the patient's operation: the first 30 cases were defined as the early cases and the subsequent 30 cases as the late cases. Main Outcome Measure(s) Operating time, perioperative complications, and surgical outcome. Univariate and multivariate analyses for risk factors with recurrence of disease. Result(s) The two groups were similar in patient characteristics. There was a reduction in the rate of laparoconversion, operating time, estimated amount of blood loss, cases with incomplete removal, and recurrence rate with increasing surgeon's experience. Surgical completeness was significantly associated with recurrence of disease. Conclusion(s) A learning curve is demonstrated in the conservative laparoscopic management of patients with rectovaginal endometriosis. After gaining experience in performing 30 cases, the recurrence rate is significantly reduced.

Hirsutism in young women is not uncommon. Several drugs have been investigated as treatment and have been largely ineffective or inconsistent although cosmetic measures have been achieved in some patients. Previous studies have suggested that flutamide and other nonestrogenic antiandrogen agents may be effective in patients with hirsutism. However, severe adverse effects such as liver toxicity limit their clinical usefulness. Reports addressing this issue have been either short-term studies (6-12 months) or had a small sample size. This prospective study assessed the safety and tolerability of long-term flutamide treatment in hirsute women. The participants were 93 women with moderate to severe hirsutism. Women who fulfilled inclusion criteria (n = 83) received either flutamide 250 mg/d alone (n = 27) or combined with a fixed dose of an oral contraceptive containing 0.020 mg of ethinyl estradiol and 0.15 mg of desogestrel (n = 56) for 84 months. Baseline and treatment data for both groups was very similar and were pooled in the final analysis. Each patient was evaluated for efficacy, safety and tolerability at 6 and 12 months follow-up, and at yearly intervals until the end of the study. Self-perception of therapeutic effect was rated by the patients using a visual analog scale. Tolerability and patient satisfaction were determined by use of questionnaires. Compared with basal values, treatment with flutamide produced a significant progressive decrease in hirsutism after 6 months of treatment (P < 0.001). Improvement in hirsutism scores was maximal at 12 months and maintained at this level throughout the 84-month study period. At follow-up, 34 patients (40.96%, 34/83) had one or more adverse events and 28 (33.73%, 28/83) presented with at least one adverse effect possibly related to flutamide treatment. Twenty patients (24.09%, 20/83) left the study due to intolerance or adverse effects requiring discontinuation of the drug. In total, 39 women (47%, 39/83) withdrew from the study during follow-up. Among those remaining in the study, self-perception of therapeutic efficacy and satisfaction with effects of therapy was high at both 6 and 84 months and none reported dissatisfaction of any type. These findings showing the long-term effectiveness of flutamide for hirsutism are consistent with data from short-term studies but further demonstrate the high incidence of adverse effects and poor treatment compliance.

Objective To evaluate the effect of FSH levels in the development of human osteoporosis. Design Case-series study. Setting Gynecology department in a teaching hospital. Patient(s) A total of 8 women diagnosed with Kallman syndrome (KS) were compared with 11 with Turner syndrome and 11 with pure gonadal dysgenesia (GD, karyotype 46,XX). Intervention(s) We assessed the pituitary–gonadal axis, bone turnover markers, bone mass, and patient characteristics. Main Outcome Measure(s) Bone mineral density as assessed by dual-energy X-ray absorptiometry, plasma FSH, LH, E 2 , osteocalcin (BGP), and urinary type I collagen cross-linked N -telopeptide. Other biochemical markers included 25-hydroxyvitamin D, as well as parathyroid hormone and urine concentration of calcium and creatinine. Result(s) In girls with Turner syndrome and GD, FSH (64.03 ± 29.2 and 90.08 ± 22.41 mIU/mL, respectively) and LH (45.29 ± 11.90 and 48.83 ± 12.44 mIU/mL, respectively) levels were significantly higher compared with those observed in girls with KS (FSH: 1.87 ± 0.64 and LH: 1.02 ± 0.57), whereas no differences were detected in E 2 or bone marker levels. Bone mineral density correlated positively with FSH levels but not with E 2 ; however, after adjusting for previous growth-hormone therapy, these differences were not found. In addition, bone mineral density in spine and total hip was significantly lower in patients with KS. Conclusion(s) Follicle-stimulating hormone does not appear to have a major role in the development of bone loss in young women with primary amenorrhea.

Objective To quantify p27 messenger RNA (mRNA) levels in human arrested and normally developing embryos and nonfertilized oocytes to determine whether the p27 protein abundance, reported in cleavage-stage embryos exhibiting developmental arrest, is regulated at the mRNA expression level. Design Real-time reverse transcription quantitative polymerase chain reaction was used to quantify the expression of p27 in three samples: arrested embryos (group A, n=29), normally developing embryos (group D, n=34), and nonfertilized oocytes (group O, n=20). Setting Research laboratory working closely with a clinical IVF practice. Patient(s) Oocytes and embryos were obtained from patients undergoing assisted fertilization. Intervention(s) None. Main Outcome Measure(s) Quantification of mRNA transcripts. Result(s) The amount of p27 mRNA was statistically significantly higher in group A (mean ± SEM, 86,143 ± 42,496 relative units [RU]) compared with groups D (10,680 ± 3,850 RU) and O (3,555 ± 1,458 RU). Furthermore, in a group of 13 two- to four-cell arrested embryos, high levels of p27 mRNA (51,481 ± 31,120 RU) were found in comparison with the nonfertilized oocyte group (3,555 ± 1,458 RU). Conclusion(s) Cleavage-stage human embryos exhibiting developmental arrest show increased p27 mRNA expression. This probably is due to increased transcriptional activity.

To evaluate the effects of recombinant human luteinizing hormone (rhLH) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age.Prospective randomized study.University teaching hospital.A total of 120 consecutive normogonadotropic infertile womenor = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment.Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone (rhFSH) and rhLH (group 1, n = 60) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH, or with rhFSH alone (group 2, n = 60).Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI outcome.The mean number of intermediate (10-14 mm) and large (14-18 mm) but not leading (or = 18 mm) follicles was significantly lower in group 1 on the day of hCG injection. The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1. However, the number of patients having embryo transfer (n = 55 in both treatment groups), the number and quality of embryos replaced, the implantation rate (20.6% vs. 21.7%) and clinical pregnancy rates per embryo transfer (44% vs. 45%) were similar in groups 1 and 2.The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies (ARTs).

Halving the standard daily dose of triptorelin at the start of ovarian stimulation in down-regulated women stimulated with recombinant FSH is enough for pituitary suppression and was associated with higher LH serum concentrations in the follicular phase. However, this did not translate into higher serum concentrations of androstenedione and E2 and had no significant effect on ovarian response and the outcome of IVF/intracytoplasmic sperm injection.

Objective To determine the prevalence of markers of thrombophilia in patients with severe ovarian hyperstimulation syndrome (OHSS) and to evaluate the cost-effectiveness of screening for factor V Leiden and prothrombin G20210A mutations in women entering an IVF program. Design Case–control study and cost-effectiveness analysis. Setting University teaching hospital. Patient(s) Women undergoing controlled ovarian hyperstimulation for IVF complicated by severe OHSS (group 1, n=20), women undergoing controlled ovarian hyperstimulation for IVF without development of severe OHSS (group 2, n=40), and healthy control subjects (group 3, n=100). Intervention(s) Investigation of markers of thrombophilia. Estimate of number of IVF patients needed to detect a case of severe OHSS and thrombosis associated with thrombophilia genetic mutation was calculated from the available data. Main outcome measure(s) Blood samples were analyzed for inherited (resistance to activated protein C due to the factor V Leiden mutation; prothrombin G20210A mutation; deficiencies in antithrombin, protein C, and protein S) and acquired (presence of circulating lupus anticoagulants and/or anticardiolipin antibodies; deficiencies of antithrombin and protein S; acquired protein C resistance) markers of thrombophilia. The cost of preventing one thrombotic event in a patient developing severe OHSS after IVF and having factor V Leiden or prothrombin G20210A mutations was calculated. Result(s) None of the OHSS patients or controls had antithrombin, protein C, or free protein S deficiencies. All of them tested negative for antiphospholipid antibodies. No patient in group 1 had the factor V Leiden or prothrombin G20210A mutations. The prothrombin G20210A mutation was detected in 1 out of 40 patients (2.5%) in group 2. Both factor V Leiden and prothrombin G20210A mutations were detected in two of the control subjects (2%) (group 3). The estimated cost of preventing one thrombotic event arising as a consequence of screening for factor V Leiden and prothrombin G20210A mutation is a minimum of $418,970 and $2,430,000, respectively. Conclusion(s) The prevalence of thrombophilia is not increased in women with severe OHSS. Screening for V Leiden and prothrombin G20210A mutation in an IVF general population is not cost-effective.

Objective To investigate the predictive value of ultrasonographic parameters as prognostic indicators of implantation after IVF when measured on the day of embryo transfer. Design Comparative, observational study. Setting University teaching hospital. Patient(s) Two hundred eighty patients undergoing IVF. Intervention(s) Ovarian stimulation, IVF. Main outcome measure(s) Variables related to patients' clinical characteristics, treatment characteristics, ovarian response, ovum retrieval, outcome of IVF and ICSI, embryo transfer, ultrasonographic and Doppler endometrial measurements, and uterine blood flow that have been proposed as potential predictive factors of implantation. All transvaginal ultrasonographic assessments were performed on the day of embryo transfer. Result(s) Among 240 patients finally evaluable, 67 (group 1) became pregnant after IVF, and 173 (group 2) failed to conceive. The 111 nonpregnant patients who had the same embryo score per replacement (group 3) as did patients in group 1 were selected for comparison purposes. The only significant differences between groups 1 and 3 were the type A endometrium and the absence of a protodiastolic notch in the uterine arteries, both of which were more frequently found in group 1. However, a considerable overlap existed between conception and nonconception cycles regarding both variables. Conclusion(s) Ultrasonographic parameters as predictors of implantation in assisted reproduction have a limited value in the clinical setting.

Objective: To assess the long-term efficacy of intraperitoneal (IP) and subcutaneous (SC) ovarian autotransplantation in rats. Design: Experimental animal study. Setting: Unit of Experimental Research, Barcelona University School of Medicine. Animal(s): Female syngeneic Lewis rats aged 14 weeks. Intervention(s): Group A, control group undergoing ovariectomy (n = 15); group B, undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In groups B and C, five animals were killed and their ovaries removed for morphometric analysis at 30 days after transplantation; five additional animals were killed at 180 days, and the remaining five animals were killed at 360 days. Main Outcome Measure(s): Ovarian morphometric analysis and serial measurement of E 2 and FSH serum levels. Result(s): The mean number of antral follicles in the control group A was significantly higher than that observed in the ovarian grafts collected and examined 30 days after grafting in rats from groups B and C, but the mean granulosa cell area was significantly higher in both transplantation groups than in controls because of ovarian follicular hyperplasia. Histological examination of ovaries removed at 6 and 12 months after grafting in groups B and C showed increasing degrees of fibrosis, loss of primordial follicles, and the presence of epithelial cysts. In groups B and C, from day 30 after surgery onward, serum E 2 was significantly higher and FSH significantly lower, respectively, than in group A. E 2 and FSH patterns in groups B and C were similar throughout the study period. Conclusion(s): Heterotopic ovarian transplantation without vascular pedicle in rats is characterized by follicular hyperplasia endocrinologically functional, followed by progressive loss of follicles in heterotopic ovarian autografts.

Objective To determine the effectiveness of immunotherapy with high-dose IV immunoglobulin preceding IVF-ET for patients with repeated failure of ET. Design Prospective, observational. Setting Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona, a tertiary care setting. Patients Twelve consecutive tubal infertility patients experiencing repeated unexplained IVF-ET failure including at least three ETs replacing three to four fresh embryos each. Two women shared three or more human leukocyte antigens (HLA) with the husband. Intervention During the subsequent new IVF-ET cycle, each patient received 400 mg/kg IV immunoglobulin daily for 5 days during ovarian stimulation, that is, 5 to 7 days before ET. Main Outcome Measures Clinical pregnancies. Results No implantation occurred. There were no side effects. Conclusions High-dose IV immunoglobulin is not a useful tool for IVF-ET failure.

Objective To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. Design Retrospective cohort study. Setting Tertiary-care university hospital. Patient(s) Nine hundred forty-seven natural cycles carried out in 320 patients. Intervention(s) Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. Main Outcome Measure(s) Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. Result(s) Among the three age groups analyzed (≤35 years, 36–39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88–0.98). Conclusion(s) NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.

Objective To produce age-related normograms for serum antimullerian hormone (AMH) level in infertile women without polycystic ovaries (non-PCO). Design Retrospective cohort analysis. Setting Fifteen academic reproductive centers. Patient(s) A total of 3,871 infertile women. Intervention(s) Blood sampling for AMH level. Main Outcome Measure(s) Serum AMH levels and correlation between age and different percentiles of AMH. Result(s) Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. We found that the curves of AMH by age for the 3rd to 50th percentiles fit the model and appearance of linear relation, whereas the curves of >75th percentiles fit cubic relation. There were significant differences in AMH and FSH levels and in antral follicle count (AFC) among women aged 24–33 years, 34–38 years, and ≥39 years. Multivariate stepwise linear regression analysis of FSH, age, AFC, and the type of AMH kit as predictors of AMH level shows that all variables are independently associated with AMH level, in the following order: AFC, FSH, type of AMH kit, and age. Conclusion(s) Age-related normograms in non-PCO infertile women for the 3rd to 97th percentiles were produced. These normograms could provide a reference guide for the clinician to consult women with infertility. However, future validation with longitudinal data is still needed.

Objective To compare two gonadotropin-releasing hormone agonists (GnRH-a), buserelin acetate and leuprolide acetate [LA], used in combination with gonadotropins in ovarian stimulation for in vitro fertilization (IVF). Design Randomized prospective study. Setting Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona. Patients Thirty-five pairs of IVF patients who were matched on age, indication, and number of attempts. These women were randomized to receive either buserelin acetate plus gonadotropins (group B) or LA plus gonadotropins (group L). Main Outcome Measures Luteolysis, ovarian response, and IVF outcome. Results The mean time for total ovarian arrest and the total dose of gonadotropins and estradiol levels on the day of human chorionic gonadotropin administration were similar in the two groups of patients. The number of follicles punctured, the number of oocytes retrieved, and the percentage of mature oocytes in group L were significantly higher. The number of embryos suitable for replacement and cryopreservation was higher in group L compared with group B approaching statistical significance. Conclusion Our results warrant further studies to compare different GnRH-a as therapeutic tools in IVF.

Objective To investigate the usefulness of day-5 inhibin B and antral follicle count (AFC) in predicting ovarian response and live birth in the first cycle of assisted reproduction. Design Prospective c ohort study. Setting University hospital. Patient(s) Ninety-eight infertile women treated with in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) comprising 72 normal responders and 26 poor responders. Intervention(s) Ovarian stimulation with gonadotropin-releasing hormone agonist-gonadotropin treatment. Main Outcome Measure(s) Basal ultrasonographic (AFC, total ovarian volume) and basal (follicle-stimulating hormone, estradiol, and inhibin B) and stimulation day-5 (estradiol, inhibin B) hormone parameters. Result(s) The AFC had the best predictive value among the basal variables for outcome of ovarian stimulation. Among the dynamic hormone measurements, day-5 inhibin serum measurement emerged as the best predictive variable of poor response in IVF–ICSI cycles, but it was not statistically significantly better than basal AFC. The association of day-5 inhibin B with live-birth rate was statistically significant and stronger than the effect of any other variable investigated. Conclusion(s) Basal AFC and day-5 inhibin B have similar predictive properties for ovarian response in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression, but day-5 inhibin B is a superior predictor of live birth.

Antiphospholipid syndrome patients with recurrent miscarriage have an impairment in fibrinolysis demonstrated by prolonged clot lysis time (CLT) that cannot be attributed to differences in thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels. Patients with unexplained recurrent miscarriage have an impairment in fibrinolysis demonstrated by increased CLT, that can be at least partly explained by higher TAFI antigen levels.

Many patients who receive co-treatment with GnRH agonists (GnRH-a) during chemotherapy treatment preserve their ovarian function and are at risk of unintended pregnancies. Therefore, it is important to offer them effective contraception. Also, pregnancies occurring after cancer therapy in women who received GnRH-a are not associated with adverse neonatal outcomes.

Objective To determine whether the presence of protamine 2 precursors (pre-P2/P2 ratio) and the protamine 1 to protamine 2 ratio (P1/P2) are related to the assisted reproduction outcome. Design Prospective study. Setting Assisted Reproduction Unit and University laboratory. Patient(s) One hundred two infertile patients undergoing treatment at the Assisted Reproduction Unit of the Hospital Clinic of Barcelona. Intervention(s) Intracytoplasmic sperm injection (ICSI) and/or IVF treatment of the infertile patients, sperm protamine analysis through electrophoresis and densitometry, and pre-P2 analysis through Western blot. Main Outcome Measure(s) The presence of protamine 2 precursors (pre-P2/P2 ratio), sperm P1/P2 ratio, fertilization rates by IVF and/or ICSI, and pregnancy outcome. Result(s) Pre-P2/P2 and P1/P2 ratios are positively associated with the pregnancy rate. In addition, the P1/P2 ratio is positively associated with the proportion of embryos obtained by IVF, but not by ICSI. The pre-P2/P2 ratio was not related to the fertilization rate. Conclusion(s) Decreased pre-P2/P2 and P1/P2 ratios are related to a poor pregnancy outcome, but not with the proportion of embryos obtained after ISCI.

Objective: To present a case of IVF failure evaluated by fluorescence in situ hybridization (FISH). Design: Case report. Setting: Research university laboratory and clinical IVF laboratory. Patient(s): An infertile couple with recurrent IVF failure. Intervention(s): Fluorescence in situ hybridization study of the complete cohort of "zygotes" obtained at the third IVF attempt. Main Outcome Measure(s): Fluorescence in situ hybridization studies of chromosomes X, Y, 13, 18, and 21. Result(s): All the recovered putative zygotes were abnormal for the expected ploidy, presumably as a result of abnormal oocytes. Conclusion(s): Fluorescence in situ hybridization techniques represent a promising approach to analyze zygotes that fail to divide normally in vitro and eggs that fail to become fertilized. In cases of recurrent IVF failure, the results of FISH could be used to counsel couples and thus to help them choose among methods other than IVF for assisted reproduction.

Objective To evaluate the effect of intranasal continuous combined hormone therapy on serum lipids and leptin levels in healthy postmenopausal women. Design Multicenter, double-blind, double-dummy, randomized, controlled study conducted in parallel groups. Setting Outpatient clinics of three Spanish hospitals and two private health centers. Patient(s) A total of 333 healthy postmenopausal women aged 40 to 75 years. Intervention(s) Women were randomly allocated to either one of three different doses of norethisterone (50 μg/day, 175 μg/day, or 550 μg/day) continuously combined with a fixed dose of 17β-estradiol (350 μg/day) for nasal administration, or 17β-estradiol at 2 mg/day combined with oral norethisterone acetate at 1 mg/day. Main Outcome Measure(s) Serum lipid, glucose, and leptin levels were assessed at baseline and after 12, 24, 36, and 52 weeks of treatment. Result(s) Overweight women (body mass index >25 kg/m 2 ) had higher baseline leptin levels, but these levels increased in all groups across the study unrelated to body mass index. Both intranasal and oral therapy had the effect of increasing the levels of leptin after 24 weeks in healthy postmenopausal women. As expected, total cholesterol and low-density lipoprotein cholesterol levels decreased and high-density lipoprotein levels increased in the four groups. Conclusion(s) Body mass index is a strong determinant of serum leptin levels in healthy postmenopausal women; serum leptin increased in all the hormone therapy regimes.

Objective To determine prospectively the effectiveness in clinical practice of a prediction model for high-order multiple pregnancies (HOMP) (triplets or more). Design Prospective study. Setting University teaching hospital. Patient(s) Eight hundred forty-nine consecutive infertile patients undergoing a total of 1,542 treatment cycles. Intervention(s) Gonadotropin ovarian stimulation or induction of ovulation without IVF Main outcome measure(s) Observed and predicted overall pregnancy rates and the incidence of HOMP. Result(s) The use of the prediction model (implying cancellation of all cycles at high risk for HOMP) would result in an 8% (95% confidence interval, 6.8%–9.2%) reduction of overall pregnancy rate but also in a 285% (95% CI, 279%–291%) reduction of HOMP. Conclusion(s) By using our prediction model, it was possible to maintain a low risk of HOMP with a good pregnancy rate in patients receiving gonadotropin ovarian stimulation or induction of ovulation without IVF.

Objective To investigate the oocyte quality in patients with severe ovarian hyperstimulation syndrome (OHSS). Design Self-controlled clinical study. Setting University teaching hospital. Patient(s) Twenty-two patients from our assisted reproductive technology (ART) program who developed severe OHSS during their first controlled ovarian hyperstimulation for IVF or intracytoplasmic sperm injection (ICSI) (OHSS cycles) during a period of 10 years and had a second ART attempt performed in our center in which OHSS did not develop (control cycles). Intervention(s) IVF and ICSI. Main outcome measure(s) Oocyte yield and quality, fertilization rate, embryo yield and quality, implantation rate, and pregnancy rate. Result(s) The total number of oocytes retrieved and the mean number of metaphase II oocytes were significantly higher in patients with OHSS than in control cycles. Fertilization rates were similar in both groups of ART cycles, and thus the number of viable embryos were significantly higher in OHSS cycles. Implantation and pregnancy rates were similar in OHSS and control cycles. Oocyte and embryo yield and quality were similar in early and late OHSS. Oocyte yield and quality, embryological outcome, and implantation and pregnancy rates were similar in patients with and without polycystic ovarian syndrome (PCOS) both in cycles developing OHSS and control cycles. Conclusion(s) Oocyte quality is not compromised in severe OHSS cycles irrespective of whether patients had or did not have PCOS.

Objective To investigate the effect on embryo transfer (ET) success of air loaded into the transfer catheter to bracket the embryo-containing medium. Design Prospective, randomized study. Setting University teaching hospital. Patient(s) One hundred two consecutive patients undergoing ET after IVF. Intervention(s) In group 1 (n = 52), embryos were loaded as follows: 200 μL of air in the syringe, 100–125 μL of air in the proximal part of the catheter, 20–25 μL of medium containing the embryos to be transferred, and 10 μL of air at the tip of the catheter. In group 2 (n = 50), the syringe and the entire catheter were filled with medium and the embryo-containing medium (20–25 μL) was aspirated without being bracketed by air spaces. Main outcome measure(s) Implantation and pregnancy rates. Result(s) No differences were found between groups 1 and 2 with respect to implantation and pregnancy rates. Conclusion(s) The air loaded into the transfer catheter to bracket the embryo-containing medium has no negative effect on ET success.

Objective To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome. Design Prospective, randomized clinical trial. Setting University teaching hospital. Patient(s) Thirty IVF patients. Intervention(s) Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively). Main outcome measure(s) Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle. Result(s) Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH. Conclusion(s) Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.

Objective: To characterize the chronology of hemodynamic changes in in vitro fertilization (IVF) cycles and its relationship with circulating ovarian steroids, cytokines, and their mediator nitric oxide. Design: Prospective, cross-sectional study. Setting: University teaching hospital. Patient(s): Eighty-eight IVF patients. Intervention(s): Ovarian stimulation with FSH under pituitary suppression. Main Outcome Measure(s): Circulating levels of estradiol, progesterone, nitrite/nitrate, interleukin-6, vascular endothelial growth factor, tumor necrosis factor α, aldosterone, norepinephrine, as well as measurements of plasma renin activity and mean arterial pressure. Result(s): The maximal stimulation of the renin-aldosterone and sympathetic nervous systems was seen 7 days after hCG administration, although values still remained elevated over normal control values on day of hCG + 11. Mean arterial pressure in IVF patients remained significantly reduced throughout the luteal phase. Changes in the stimulation of the renin-aldosterone system correlated temporally with progesterone but not estradiol levels. No significant changes were observed in circulating concentrations of cytokines investigated or nitric oxide. Conclusion(s): The circulatory changes and the homeostatic activation of the renin-aldosterone system and sympathetic nervous system that consistently develop in patients undergoing controlled ovarian hyperstimulation for IVF is a feature associated with the luteinization process. These hemodynamic changes occur in the absence of variations in the circulating levels of cytokines potentially involved in ovarian hyperstimulation syndrome.

Objective: To investigate the effects of long-term down-regulation (4 months) used in combination with gonadotropin ovarian stimulation for IVF-ET. Design: Prospective randomized study. Setting: Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona, a tertiary care setting. Patient(s): Thirty pairs of IVF patients who were matched for age, indication for IVF, and number of attempts. Intervention(s): Women were randomized to receive a standard long protocol of SC leuprolide acetate (n = 30, group L) or a monthly injection of leuprolide acetate depot for 4 months (n = 30, group D) before gonadotropin stimulation. Main Outcome Measure(s): Ovarian response and IVF outcome. Result(s): Days of ovarian stimulation, follicular recruitment and growth during gonadotropin treatment, and the endometrial thickness on the day of hCG administration were similar for the 2 groups of IVF patients. However, the serum concentration of E 2 was significantly higher in group L even though group D received a higher total dose of gonadotropins. The number of follicles punctured, the number of oocytes retrieved, the number of oocytes fertilized, the number of embryos suitable for replacement and cryopreservation, the number of patients with ET, and implantation and clinical pregnancy rates were similar for groups L and D. However, the percentage of metaphase II oocytes was significantly higher in group L than in group D. Conclusion(s): Long-term down-regulation does not improve pregnancy rates in a general IVF program.

Objective To determine the plasma levels of immunoreactive endothelin in patients with severe ovarian hyperstimulation syndrome (OHSS). Design Prospective longitudinal study. Setting Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona, a tertiary care setting. Patients Sixteen IVF patients with severe OHSS. Main Outcome Measures Measurement during the syndrome and 4 to 5 weeks after recovery of the following: mean arterial pressure, hematocrit, plasma renin activity, plasma aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic peptide, and immunoreactive endothelin concentrations. Results During the syndrome patients showed decreased mean arterial pressure (70.0 ± 1.1 versus 85.2 ± 1.6 mm Hg), increased mean hematocrit values (45.5% ± 1.1% versus 38.1% ± 0.4%), oliguria (630.6 ± 40.7 versus 1,306.2 ± 43.9 mL/d), and very high plasma levels of renin (36.0 ± 9.1 versus 1.2 ± 0.08 ng/mL per hour), aldosterone (190.6 ± 28.4 versus 14.8 ± 1.5 ng/dL), norepinephrine (602.1 ± 91.0 versus 220.5 ± 12.1 pg/mL), antidiuretic hormone (4.1 ± 0.7 versus 1.0 ± 0.1 pg/mL), and atrial natriuretic peptide (10.9 ± 1.6 versus 4.7 ± 0.2 fmol/mL). Immunoreactive endothelin plasma levels were increased significantly during OHSS (8.9 ± 0.9 versus 3.9 ± 0.2 pg/mL) and all patients had elevated values during the syndrome. Conclusions Circulating plasma levels of immunoreactive endothelin are elevated in patients with severe OHSS in parallel with other neurohormonal vasoconstrictor systems. It may represent a homeostatic response to maintain blood pressure.

Major histocompatibility differences between mother and fetus may facilitate implantation and maintenance of pregnancy. Thus, we have investigated the compatibility of HLAs in couples with three successive failed IVF-ET cycles. The study couples (n = 15) shared a statistically greater number of HLAs than IVF couples achieving a viable pregnancy with their first IVF-ET attempt (n = 15) and a control group of 100 fertile couples. No difference between fertile and infertile control couples was observed regarding HLA sharing. Thus, we conclude that some cases of unsuccessful ETs after IVF might be caused by underlying close histocompatibility between partners.

Objective To assess the prevalence of human immunodeficiency virus (HIV) antibody in infertility. Design Prospective cross-sectional blind study. Setting An infertility clinic in Barcelona. Patients Three hundred thirty-five consecutive patients (308 infertile women and 27 spontaneous recurrent aborters) were seen between January 1989 and May 1990. Main Outcome Measure Human immunodeficiency virus serostatus. Results The rate of seropositivity in the group of patients studied was 0.3% (95% confidence interval 0% to 0.9%). Conclusion Further studies are desirable to establish the value of routine HIV testing in infertility patients as a population of women actively seeking pregnancy.

Fifteen infertile women with inadequate luteal phase, histologically documented in at least two separate cycles, and normal midluteal plasma levels of progesterone (greater than or equal to 10 ng/mL), estradiol (70 to 300 pg/mL), and prolactin (less than 20 ng/mL) received "pure" follicle-stimulating hormone (pFSH), 150 IU intramuscularly, for 4 days (days 1 to 4 of the cycle). The endometrial defect was corrected in 7 of the 15 (46.7%) patients during the first treated cycle. Hormonal levels were similar in control and treatment cycles. Two of 5 patients with no additional infertility factors except luteal phase deficiency (LPD) became pregnant and carried to term singleton pregnancies. In 5 additional infertile patients with normal luteal function as assessed by endometrial histological study (2 cycles) and hormone measurements (first study cycle), a third biopsy was performed in a consecutive cycle under pFSH administration. In no case was the normal secretory pattern impaired. It is concluded that (1) some forms of LPD may be successfully treated by early follicular pFSH therapy and (2) pFSH does not alter the normal endometrial secretory pattern.

Hyperprolactinemia was detected in 15 of 130 infertile patients (11.5%) with regular menstrual cycles and no galactorrhea who underwent luteal phase evaluation by basal body temperature (BBT), plasma estradiol (E2), and progesterone (P) determination, and endometrial biopsy (repeated in a later cycle when the first was defective). Luteal phase length and plasma levels of P and E2 were similar in the hyperprolactinemic and normoprolactinemic patients. Moreover, a significantly higher incidence of inadequate luteal phase, histologically documented, was found in the normoprolactinemic group. It is concluded that the usefulness of plasma prolactin (PRL) determination in the evaluation of luteal function in infertility is scanty and that most histologically documented cases of luteal phase defects occur with euprolactinemia.

Twenty infertile patients being treated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) for induction of ovulation, with a defective endometrial secretory pattern despite normal plasma levels of progesterone, estradiol, and prolactin, were entered into treatment plans on a random basis involving the following: CC-hCG plus dehydrogesterone (group 1), and CC-hCG (group 2). Success rates were similar in both groups (20% and 30%, respectively), based on a corrected endometrial defect during the second treated cycle. It is concluded that progestational agents are of low therapeutic value in endometrial luteal phase deficiency induced by CC.

The effect of dehydrogesterone upon corpus luteum function as reflected by plasma progesterone levels was investigated in eight healthy women. No significant difference was found between control cycles and treated cycles when dehydrogesterone, 20 mg daily, was given orally for 10 days after ovulation.

Thirty-three infertile patients presenting spontaneous ovulatory cycles with long follicular phases (greater than or equal to 20 days) underwent a luteal function evaluation by basal body temperature, plasma progesterone (P), estradiol, and prolactin determination, and endometrial biopsy study. An endometrial luteal phase deficiency (LPD) was detected in 13 patients (39.4%), although in 10 of them (77%) P levels were normal. This study shows a high incidence of endometrial LPD among cycles with delayed ovulation and that in cases of LPD related to abnormal folliculogenesis, the endometrium is a better indicator than plasma P.

Forty-four infertile patients with inadequate luteal phase histologically documented in at least two separate cycles and normal plasma levels of progesterone (P), estradiol (E2), and prolactin (PRL) were entered into treatment plans on a random basis involving at least 3 months of each of the following: P vaginal suppositories, dehydrogesterone, and no treatment. Success rates were similar for P (62.5%) and dehydrogesterone (68.7%), based on a corrected endometrial defect during the fourth treated cycle or when a term pregnancy was achieved. However, these figures are significantly different (P less than 0.001) when compared with 16.6% of the control group. In ten additional infertile patients with normal luteal function as assessed by endometrial histologic study and hormone measurements, a second biopsy was performed in a consecutive cycle under dehydrogesterone administration. In no case was the normal secretory pattern impaired. It is concluded that (1) both P and dehydrogesterone can be used to advantage in the treatment of luteal phase defects, and (2) therapy with dehydrogesterone does not alter the normal pattern of endometrial secretion.

We studied endometrial luteal phase in specimens from 660 biopsies done in 300 patients from our infertility clinic. A minimum of two (240 women) or three (60 women) endometrial biopsy specimens from separate cycles were taken regardless of the previous histologic findings in all patients. Statistical analysis of results by the McNemar and the Cochran Q tests for the significance of changes leads us to conclude that a minimum of two, and even three, endometrial biopsy specimens are needed for diagnosis of luteal phase deficiency.