Endometrial receptivity tests in reproduction: a SWOT analysis.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual 'window of implantation', providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential.

The role of thrombophilias in reproduction: A swot analysis.

Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure.

Impact of chronic endometritis in infertility: a SWOT analysis.

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard.

Second-generation preimplantation genetic testing for aneuploidy in assisted reproduction: a SWOT analysis.

Second-generation preimplantation genetic testing for aneuploidy (PGT-A 2.0) in patients with an unfavourable reproductive and IVF prognosis is becoming common practice, with the aim of improving reproductive outcomes. However, there is still no clear evidence on the possible advantages and drawbacks with regard to this procedure. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Current evidence suggests that PGT-A 2.0 should not at present have an indiscriminate application, but it might be indicated in cases in which the risk of aneuploidy is increased.

Transmyometrial embryo transfer as a useful method to overcome difficult embryo transfers - a single-center retrospective study.

OBJECTIVE: Pregnancy after an embryo transfer depends largely on embryo quality, endometrial receptivity, and the technique used in the embryo transfer. Embryo transfers have been reported as inevitably traumatic and difficult for 5-7% of patients in assisted reproduction treatment. In these cases, transmyometrial embryo transfer should be considered as a suitable method to overcome difficult embryo transfers. The aim of this study was to report our experience with this technique and analyze its causes, results and complications. METHODS: Since 1993, 39 women (40 cycles of assisted reproductive technology treatment) were submitted to transmyometrial embryo transfers in our center. The procedures were carried out as described by the Towako group. RESULTS: The enrolled female patients had a mean age of 34 years and a mean baseline FSH level of 6.89 IU/mL. The median number of retrieved oocytes was 7.50 and a mean of 2.63 embryos were transferred. Implantation rate was 9.5%. With respect to clinical results, pregnancy and miscarriage rates were 25% and 30%, respectively. Since there were two twin pregnancies, the live birth rate was 22.5% (9/40). No major complications were reported. CONCLUSION: Transmyometrial embryo transfer can and should be an option in cases of difficult/impossible transcervical embryo transfer.

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

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.

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

OBJECTIVE: 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. DESIGN: Retrospective case series and cost analysis study using a decision-tree model. SETTING: University hospital. POPULATION: 496 consecutive patients with ovarian hyperstimulation syndrome treated in our center from 1991 to 2010. METHODS: All patients were treated with a conservative medical approach: (a) conservative outpatient approach: bed rest and a low-sodium diet or (b) hospitalized patients: bed rest, low-sodium diet, 20% albumin (60 g/day) and furosemide (20 mg/8 h). MAIN OUTCOME MEASURES: Percentage of admissions, length of hospital stay and readmissions. Total cost of each therapeutic approach. RESULTS: (a) Conservative outpatient approach (n = 377): all cases solved without admission. (b) Hospitalized patients with conservative medical treatment (n = 119): 2.8 days of mean hospital stay, no patient required paracentesis or admission to intensive care unit. Readmissions: Five patients (4.2%) resolved on restarting medical treatment. (c) Cost-analysis comparison: Cost of the outpatient approach with paracentesis: US$980 (range US$519-3557). Cost of conservative medical treatment: US$570 (range US$232-1640). CONCLUSIONS: Ovarian hyperstimulation syndrome can be safely managed with a conservative medical approach, which was not found to be more expensive than outpatient management with paracentesis.

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.

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.

Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis.

A systematic review and meta-analysis was performed to evaluate the effect of transdermal testosterone preceding ovarian stimulation in women with poor ovarian response undergoing IVF. Studies comparing pretreatment with transdermal testosterone versus standard ovarian stimulation among poor responders were included. The main outcome assessed was live birth. Three trials were included (113 women in the testosterone group, 112 in the control group). Testosterone-treated women achieved significantly higher live birth rate (risk ratio, RR, 1.91, 95% CI 1.01 to 3.63), clinical pregnancy rate (RR 2.07, 95% CI 1.13 to 3.78) and required significantly lower doses of FSH (RR -461.96, 95% CI -611.82 to -312.09). However, differences observed in clinical pregnancy per embryo transferred were not statistically significant (RR 1.72, 95% CI 0.91 to 3.26). No differences were observed regarding number and quality of the oocytes retrieved. In conclusion, transdermal testosterone significantly increases live birth and reduces the doses of FSH required. These findings support the theoretical synergistic role of androgens and FSH on folliculogenesis. The present data should be interpreted with caution because of the small number of trials and clinical heterogeneity. The identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies. The poor response to ovarian stimulation among women undergoing IVF is of great concern in reproductive medicine. Certain modalities have been tested to improve this response to gonadotrophin stimulation, although results from some studies have shown conflicting results. Hence, a systematic review and meta-analysis was performed in order to evaluate the effect of transdermal testosterone prior to ovarian stimulation among these women with poor ovarian response. The main outcome assessed was live birth rate. In all, three trials were included, which comprehended 113 women in the testosterone group and 112 in the control group. Women that were pretreated with transdermal testosterone achieved significantly higher live birth rate and clinical pregnancy rate and required significantly lower doses of exogenous FSH as compared with controls. However, when clinical pregnancy rate was adjusted per embryo transferred differences observed were not statistically significant. No differences were observed in the number and quality of the oocytes retrieved. In conclusion, transdermal testosterone prior to ovarian stimulation significantly increases live birth and reduces the doses of FSH required among poor responders. In addition, the identification of poor responders that could especially benefit from testosterone treatment should be addressed in further studies.

Human chorionic gonadotrophin stimulation test as a predictor of ovarian response and pregnancy in IVF cycles stimulated with GnRH agonist gonadotrophin treatment: a pilot study.

BACKGROUND: Recent evidence supports a specific and broad role of androgen produced by theca cells in reproductive physiology. This pilot study evaluated the usefulness of hCG theca stimulation test in predicting ovarian response and pregnancy. METHODS: Prospective cohort study including 80 infertile women treated with IVF/ICSI. On Day 3 of the menstrual cycle preceding, the first IVF/ICSI cycle a blood sample was drawn to evaluate baseline FSH, estradiol (E(2)), 17-hydroxy-progesterone, androstenedione and testosterone levels. All women then received 250 µg recombinant hCG s.c. and underwent a second blood sampling 24 h after hCG injection to measurement steroid serum levels. RESULTS: Percentage increment of E(2) but not its precursors was significantly higher in normo-responders and pregnancy cycles than in poor responders and non-pregnancy cycles (P = 0.03 and P = 0.02, respectively) diagnostic accuracy being 67 and 75%, respectively. The percentage increase in E(2) thus still fails in as many as 33 and 25% of patients in predicting ovarian response and pregnancy, respectively. In addition, E(2) concentrations are poorly reproducible and a wide range of variation in all serum steroids investigated-including E(2)-after hCG injection was observed. CONCLUSIONS: The predictive power of the hCG test is based on E(2) but not androgen response to hCG injection. This test cannot be recommended in routine clinical practice because it is too laborious for screening purposes, shows great variability in the response obtained and its overall accuracy is not better than that reported for other available markers of ovarian reserve. The use of the currently available markers, antral follicle count and anti-Müllerian hormone, is therefore recommended.

Expression pattern of osteopontin and αvß3 integrin during the implantation window in infertile patients with early stages of endometriosis.

BACKGROUND: To study endometrial receptivity in terms of osteopontin (OPN) and αvß3 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 αvß3 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 αvß3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvß3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied. CONCLUSIONS: Endometrial OPN and αvß3 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.

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.

The effect of different hormone therapies on anti-müllerian hormone serum levels in anovulatory women of reproductive age.

OBJECTIVE: To investigate the effect of oral contraceptives (OC), metformin and ovulation induction with gonadotropins on circulating anti-müllerian hormone (AMH). DESIGN: Prospective clinical study. PATIENTS: Thirty patients with PCOS (Group 1), 15 normogonadotropic anovulatory infertile women (WHO 2) (Group 2) and 15 normoovulatory control women (Group 3). Patients in Group 1 received OC (n = 12), metformin (n = 11) or no-treatment (n = 7) for 6 months. Ovulation induction with FSH or hMG was used in Group 2. MAIN OUTCOME MEASURES: Total follicle number (TFN) and hormonal (fasting insulin and glucose, testosterone, SHBG, LH, androstenedione and AMH) measurements at baseline and during therapy. RESULTS: Basal AMH and TFN were higher in Groups 1 and 2 than in controls. Only TFN was significantly related to AMH level in Groups 1 and 2. AMH level was significantly reduced during OC treatment, and there was a trend for AMH decrease during metformin therapy. No significant changes in AMH level were observed during ovulation induction. TFN was the only parameter showing a significant positive correlation with circulating AMH over the 6-month treatment period in patients in Group 2. CONCLUSIONS: AMH is an accurate marker of the antral follicle pool in WHO-2/PCOS women but the measurement of AMH is not likely to be helpful in the management of those patients.

Osteopontin and alphavbeta3 integrin as markers of endometrial receptivity: the effect of different hormone therapies.

The osteopontin: alphavbeta3 integrin complex has been proposed as a means of distinguishing receptive from non-receptive endometrium in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. Histological dating and immunohistochemical study were performed in control and study cycles in seven groups of women including 10 subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, two different regimens of hormone replacement therapy, or no treatment. Ten healthy fertile women served as a general control group. Osteopontin and alphavbeta3 integrin expression in the human endometrium was closely related to endometrial maturation and this was irrespective of the endometrium being in-phase or out-of-phase and the hormonal treatment (or no treatment) received. In conclusion, immunohistochemical assessment of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin or the osteopontin: alphavbeta3 integrin complex as targets for the development of contraceptive approaches or the understanding of the pathogenesis of female infertility offer little benefit compared with simple histological dating.

Day-5 inhibin B serum concentrations and antral follicle count as predictors of ovarian response and live birth in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression.

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 cohort 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.

Ovarian luteinizing hormone priming preceding follicle-stimulating hormone stimulation: clinical and endocrine effects in women with long-term hypogonadotropic hypogonadism.

CONTEXT: Patients with hypogonadotropic hypogonadism (HH), who may be totally LH deficient, remain the primary clinical model for investigating the physiology of gonadotropin actions on ovarian steroidogenesis and follicular development. OBJECTIVES: Our objective was to investigate the effects of LH pretreatment on subsequent ovarian stimulation with FSH in longstanding HH women. DESIGN AND SETTING: A prospective, self-controlled study was conducted at a university tertiary-care center. PATIENTS AND INTERVENTIONS: Eight HH women (six idiopathic, two surgical) underwent ovarian stimulation with recombinant human (rh)FSH preceded or not by rhLH administration in two separate cycles. In one additional patient with idiopathic HH, pretreatment was conducted with recombinant human chorionic gonadotropin (rhCG) instead of rhLH. MAIN OUTCOME MEASURES: Follicular development and serum hormone concentrations throughout LH-FSH and FSH treatment cycles were assessed. RESULTS: Pretreatment with rhLH significantly decreased the mean threshold (daily effective) FSH dose and tended to lower the total amount of FSH required to induce follicular maturation in association with appropriate serum estradiol levels and endometrial thickness. Unexpectedly, in HH women retaining functional pituitary tissue, pretreatment with rhLH evoked a consistent elevation of serum LH levels during FSH administration, an effect that was also induced, even at higher magnitude, by pretreatment with rhCG. CONCLUSIONS: In addition to changes in FSH requirements for follicular maturation, pretreatment with rhLH/rhCG evoked unambiguous elevations in serum levels of endogenous LH during FSH treatment in HH patients with preserved pituitary function. This is suggestive of a novel regulatory loop of LH secretion involving gonadotropin-stimulated ovarian factors whose nature and physiological relevance are yet to be disclosed, ovarian-derived kisspeptins being appealing candidates.

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.

Osteopontin and alphavbeta3 integrin expression in the endometrium of infertile and fertile women.

Osteopontin and its receptor alpha(v)beta(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 alpha(v)beta(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 alpha(v)beta(3) integrin and osteopontin expression and their coexpression 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:alpha(v)beta(3) integrin complex as a marker of endometrial receptivity and implantation potential in women seems to be untenable.

Combined laparoscopic surgery and pentoxifylline therapy for treatment of endometriosis-associated infertility: a preliminary trial.

BACKGROUND: Surgical treatment has modest efficacy for the treatment of infertility associated with early-stage endometriosis. Immunomodulation with pentoxifylline is considered as a new strategy potentially useful in treating endometriosis. Thus, this study investigated the usefulness of combined laparoscopic surgery and pentoxifylline therapy in the treatment of infertility associated with minimal to mild endometriosis. METHODS: A prospective, randomized, controlled blind trial was conducted. Patients entered the study immediately after laparoscopic surgery and were randomly assigned to the treatment with either oral pentoxifylline (800 mg/day) (pentoxifylline group, n = 51) or an oral placebo (placebo group, n = 53). Patients were then observed for pregnancy for 6 months. RESULTS: Among 98 patients finally considered in the evaluation of the results, the 6 month overall pregnancy rates were 28 and 14% in the pentoxifylline and placebo groups, respectively. Thus, an absolute difference of 14% (95% CI -2 to 30) (Chi-squared test, P = 0.1) in the cumulative probability of pregnancy in 6 months after laparoscopic surgery in patients receiving pentoxifylline versus placebo post-operatively was observed. CONCLUSION: Our findings provide preliminary clinical evidence to suggest the new experimental treatment approaches, toward endometriosis, that are based on immunomodulation deserve further attention. Well-designed multicenter trials are warranted to confirm or refute our results.

Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been investigated as a marker of ovarian response to controlled ovarian hyperstimulation and as a predictor of ovarian hyperstimulation syndrome (OHSS) in IVF cycles. In most studies, serum has been used for circulating VEGF concentration measurement, but it has been suggested that plasma is the preferred medium to measure VEGF levels because of the potential contribution of VEGF released from platelets during blood clotting. This study investigated VEGF concentrations in paired serum and plasma samples from patients undergoing controlled ovarian hyperstimulation for IVF. METHODS: Serum and plasma VEGF levels, as well as the number of platelets, were measured in 30 IVF patients who comprised three study groups delineated according to the estradiol (E(2)) serum concentration reached on the day of HCG administration: 10 patients having low E(2) serum levels (<1500 pg/ml, group L), 10 patients having intermediate E(2) serum levels (1500-3000 pg/ml, group I) and 10 patients having high E(2) serum levels (>3000 pg/ml, group H). RESULTS: There was a statistically significant correlation between plasma and serum VEGF levels (rho = 0.61; P < 0.005) for the entire population studied, although serum values were higher by a factor of approximately 6-fold. No significant correlation was found between peripheral blood VEGF concentrations and serum E(2) or follicle number on HCG day or the number of oocytes collected. Similarly, paired serum and plasma VEGF measurements did not correlate with platelet count. CONCLUSIONS: Serum and plasma VEGF concentrations are strongly correlated in paired samples from infertile patients undergoing controlled ovarian hyperstimulation. However, neither serum nor plasma VEGF levels were correlated with parameters associated with ovarian follicular activity. Peripheral blood VEGF levels were not correlated with platelet count.