Gemma Casals

Transdermal testosterone may improve ovarian response to gonadotrophins in low-responder IVF patients: a randomized, clinical trial

BACKGROUND Studies in macaques have indicated that androgens have some synergistic effects with FSH on folliculogenesis. This study investigated the usefulness of pretreatment with transdermal testosterone in low-responder IVF patients. METHODS Randomized clinical trial including 62 infertile women who had a background of the first IVF treatment cycle cancelled because of poor follicular response. Patients were randomized in two treatment groups in their second IVF attempt. In patients in Group 1 (n = 31), transdermal application of testosterone preceding standard gonadotrophin ovarian stimulation under pituitary suppression was used. In Group 2 (n = 31 patients), ovarian stimulation was carried out with high-dose gonadotrophin in association with a minidose GnRH agonist protocol. The primary end-point was the incidence of low-responder patients. The main secondary outcome was the incidence of patients reaching ovum retrieval. RESULTS The percentage of cycles with low response was significantly lower in Group 1 than in Group 2 (32.2 versus 71% 95% confidence interval for the difference, 15.7-61.6; P < 0.05). The number of patients with ovum retrieval tended to be higher in Group 1 than in Group 2 (80.6 versus 58.1% P = 0.09), the difference reaching statistical significance (81.2 versus 41.1%; P < 0.05) when only patients having normal basal FSH levels (16 and 17 patients in Groups 1 and 2, respectively) were considered. CONCLUSIONS Pretreatment with transdermal testosterone may improve the ovarian sensitivity to FSH and follicular response to gonadotrophin treatment in previous low-responder IVF patients. This approach leads to an increased follicular response compared with a high-dose gonadotrophin and minidose GnRH agonist protocol.

Uterine (CD56+) Natural Killer Cells Recruitment: Association with Decidual Reaction Rather than Embryo Implantation

Whether decidual leukocyte recruitment and/or increase is primarily hormonally regulated or induced mainly by blastocyst implantation is a matter of debate. Thus, this study investigated the number and distribution of leukocyte populations, with emphasis on natural killer (NK) cells of uterine and peripheral type, within decidual tissue from women with decidualized endometrium both related and unrelated to pregnancy and those with ectopic decidua associated with intrauterine pregnancy, as well as in tubal implantation sites.

Expression pattern of osteopontin and αvβ3 integrin during the implantation window in infertile patients with early stages of endometriosis

BACKGROUND To study endometrial receptivity in terms of osteopontin (OPN) and αvβ3 integrin expression and co-expression in infertile women with early stages of endometriosis. METHODS We investigated the immunohistochemical expression and co-expression of OPN and αvβ3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject. RESULTS No statistically significant differences regarding OPN and αvβ3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvβ3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied. CONCLUSIONS Endometrial OPN and αvβ3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.

Osteopontin and αvβ3 integrin expression in the endometrium of infertile and fertile women

Abstract Osteopontin and its receptor α v β 3 integrin have recently been proposed as a major complex to promote embryo attachment, and thus they would be useful as markers of endometrial receptivity. In the current study α v β 3 integrin and osteopontin expression and co-expression in in-phase and out-of-phase endometrial biopsies from normal healthy women ( n = 12) and infertile patients ( n = 107) were investigated. Two endometrial biopsies (post-ovulatory day +6 to +8, and 4 days later) were performed during a single menstrual cycle in each subject. Oestradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling. No statistically significant difference regarding α v β 3 integrin and osteopontin expression and their co-expression was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase, infertility factors detected or whether patients became spontaneously pregnant or not. Although a co-ordinate high concentration of both glycoproteins on post-ovulatory day 8 onwards was observed, there was an evident lack of temporal co-expression of these markers during the implantation window. It is concluded that the functional significance of the osteopontin: α v β 3 integrin complex as a marker of endometrial receptivity and implantation potential in women seems to be untenable.

Ultrasonographic Diagnosis of Jarcho-Levin Syndrome at 20 Weeks’ Gestation in a Fetus without Previous Family History

Jarcho-Levin syndrome (JLS; spondylothoracic dysplasia) is a congenital disease characterized by multiple vertebral and rib malformations, causing a short trunk dwarfism commonly leading to respiratory insufficiency and death during the first years of life. We describe a case diagnosed during the second trimester routine ultrasound scan for screening of fetal anomalies without a previous family history. The fetus had a severe disorganization of the spine and ribs, skeletal kyphosis, with several hemivertebrae and a small thorax. All of the findings at postmortem examination confirmed the ultrasound features and were consistent with the JLS. To the best of our knowledge there is only one case reported in the literature of a prenatal diagnosis of the syndrome in a family with low risk for the condition.

Outcome from consecutive ICSI cycles in patients treated with recombinant human LH and those supplemented with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol

Abstract Clinical results were compared in a well-established, assisted reproduction program during the cross-over from highly purified (HP)-human menopausal gonadotropin (hMG) to rhFSH/rhLH. We included the last 33 patients treated with HP-hMG and the first 33 patients receiving rhFSH/rhLH for ovarian stimulation in their first intracytoplasmic sperm injection cycle. Patient baseline characteristics were almost identical in the two groups. Ovarian stimulation characteristics (days of stimulation, total amount of FSH administered using a modest initial loading dose of 150 IU/d, patients with oocyte retrieval) were similar for the two groups. However, the number of total and leading follicles and E2 serum levels on the human chorionic gonadotropin injection day were significantly higher in the rhFSH/rhLH group. The oocyte yield was significantly higher in the rhFSH/rhLH group as well as the number of metaphase II oocytes, difference almost reaching the statistical significance. The number of oocytes fertilized was also higher in patients receiving rhFSH/rhLH treatment. Implantation and clinical pregnancy rates were similar in both the study groups. It is concluded that in women undergoing controlled ovarian hyperstimulation under pituitary suppression for ART, the recombinant combined product containing FSH and LH in a fixed 2:1 ratio is more effective than HP-hMG in terms of follicle development, oocyte yield and quality, and fertilization rates.

Conservative medical treatment of ovarian hyperstimulation syndrome: a single center series and cost analysis study.

To present the results of a large series of patients with ovarian hyperstimulation syndrome treated with a conservative medical approach and to compare the cost of this treatment with outpatient management with paracentesis according to published data.

Evaluation of two doses of recombinant human luteinizing hormone supplementation in down-regulated women of advanced reproductive age undergoing follicular stimulation for IVF: a randomized clinical study

OBJECTIVES To evaluate the effects of mid-follicular recombinant human luteinizing hormone (rhLH) supplementation in down-regulated women of advanced reproductive age undergoing in vitro fertilization (IVF). STUDY DESIGN This was a prospective, randomized parallel-group study (allocation 1:1) including 187 normogonadotrophic infertile patients aged ≥ 35 years. Subcutaneous triptorelin was used for pituitary desensitization, and ovarian stimulation was achieved with recombinant human follicle-stimulating hormone (rhFSH) either alone (Group 1) or in combination with rhLH in one of two daily doses: 37.5 IU (Group 2) or 75 IU (Group 3). Ovarian stimulation characteristics and IVF outcome were evaluated. The main outcome was pregnancy rate. RESULTS A total of 62, 62 and 63 patients were randomized to groups 1, 2 and 3 respectively, and 56, 54 and 55 patients respectively were available for final analysis of the results. Follicular development and oocyte yield were significantly higher in group 1 patients compared with patients in groups 2 and 3. Oocyte maturity and number of oocytes fertilized were also higher in group 1 patients; this difference almost reached statistical significance. No significant difference in implantation and clinical pregnancy rates was found among the three treatment groups. CONCLUSIONS rhLH supplementation is not a useful tool for patients of advanced reproductive age in ovarian stimulation protocols using an appropriate gonadotrophin-releasing hormone agonist and a step-down regimen of rhFSH.

Efficacy and Safety of Ibuprofen Arginine in the Treatment of Primary Dysmenorrhoea

ObjectiveThe aim of this study was to evaluate the efficacy and safety of ibuprofen arginate in the treatment of patients with primary dysmenorrhoea in normal clinical practice.Study designIn this open trial, patients received an initial oral dose of ibuprofen arginine 600mg at the onset of pain, followed by the same dose every 6 hours, if necessary, with a maximum daily dose of 2400mg. The study assessed the evolution of pain intensity, rapidity of action, need for supplementary analgesics, decrease in working or school hours lost, and safety and tolerability of ibuprofen arginine treatment. Each patient was evaluated prior to inclusion in the study and after one and three cycles.ResultsFrom the 1093 recruited patients, 854 women were evaluable for safety and tolerability, and 838 for efficacy. Significant improvement in pain relief was observed 15 minutes after treatment compared with baseline values (p < 0.001). At 15 and 30 minutes the percentage of patients reporting a marked decrease in pain intensity was 82.2% and 97.6%, respectively. Additionally, a significant reduction in absenteeism from work or school (from a mean of 4.6-0.8 hours per cycle) was observed (p < 0.001). Thirty-eight patients presented with adverse events in the trial period, but only 26 subjects (3% of 854) in the adverse events cohort reported having a possible adverse event, with gastrointestinal complaints being the most frequent.ConclusionIbuprofen arginine appears to be effective, fast, safe and well tolerated in the treatment of patients with primary dysmenorrhoea.

Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer.