Abstract: BACKGROUND: Although initial studies in poor responders using GnRH antagonists have reported encouraging results, they are limited in number, only a few of them are prospective, while the majority is characterized by limited power to detect a clinically important difference. METHODS: A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which five or less oocytes were retrieved, using > or =300 IU of gonadotrophins/day. Patients were randomized by computer-generated list and treated by either the flare-up GnRH agonist protocol (n = 90) or a flexible GnRH antagonist protocol (n = 180). RESULTS: Ongoing pregnancy rate, the primary outcome measure, was significantly higher in the antagonist group compared with the agonist group (12.2 versus 4.4%, P< 0.048; difference 7.8%, 95% CI: 0.2 to 14.0). Estradiol levels on the day of hCG administration were lower in the antagonist protocol [median (interquartile range): 572 (325-839) versus 727 (439-1029) pg/ml, P = 0.018]. Clinical and biochemical pregnancy rates, fertilization and implantation rates, as well as the number of oocytes retrieved, the number of mature oocytes present, the stimulation period and the gonadotrophin dosage were not significantly different between the two groups compared. CONCLUSIONS: The flexible GnRH antagonist protocol is associated with significantly higher ongoing pregnancy rates compared with the flare-up GnRH agonist protocol in poor responders.

Abstract: BACKGROUND: Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. The number of embryos transferred, however, is a crucial parameter that needs to be considered before attempting any comparison. METHODS: An extensive literature search yielded initially 282 studies from which 8 randomized controlled trials met the inclusion criteria: (i) truly randomized design (ii) policy to transfer equal number of embryos in both the cleavage-stage and the blastocyst-stage groups and (iii) published as full text in a peer-review journal. Primary outcome was the live birth rate and secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, cancellation rate and cryopreservation rate. RESULTS: A total of 1654 patients were reviewed. Live birth rate per randomized patient was significantly higher (n = 6 studies) in patients who had a blastocyst-stage transfer as compared to patients with cleavage-stage embryo transfer [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10-1.76; P = 0.005]. Clinical pregnancy rate (OR: 1.27, 95% CI: 1.03-1.55; P = 0.02) and cancellation rate per patient randomized (OR: 2.21, 95% CI: 1.47-3.32; P = 0.0001) were significantly higher in patients with a blastocyst-stage embryo transfer as compared to patients in whom a cleavage-stage embryo transfer was performed. The cryopreservation rate was significantly higher in the cleavage-stage group (OR: 0.28, 95% CI: 0.14-0.55; P = 0.0002). CONCLUSIONS: The best available evidence suggests that the probability of live birth after fresh IVF is significantly higher after blastocyst-stage embryo transfer as compared to cleavage-stage embryo transfer when equal number of embryos are transferred in the two groups compared.

Abstract: This prospective randomized controlled pilot study was conducted in a tertiary referral university hospital to evaluate whether the administration of letrozole in the luteal phase of stimulated IVF cycles, through a decrease in oestradiol, could alter the suppressed LH levels in the luteal phase. Following oocyte retrieval, six oocyte donors aged < or = 36 years were randomized to receive either 5 mg letrozole (n = 3) or placebo (n = 3). On days 4, 7 and 10 after human chorionic gonadotrophin (HCG) administration, oestradiol levels of the letrozole group were significantly lower compared with the placebo group (P = 0.008, P =0.005 and P =0.004, respectively). LH and progesterone values were comparable between both groups at all time points measured. This study demonstrates that the addition of 5 mg of letrozole in the luteal phase of stimulated donor IVF cycles significantly alters the oestradiol levels on days 4, 7 and 10 after HCG administration for final oocyte maturation. The progesterone and LH profiles of patients treated with letrozole during the same period were not altered compared with the placebo group.

Abstract: BACKGROUND: The purpose of the present systematic review and meta-analysis was to examine whether the probability of pregnancy is increased by adding estrogen to progesterone for luteal phase support in patients treated by in vitro fertilization (IVF). METHODS: A literature search covering MEDLINE, EMBASE, CENTRAL, meeting proceedings and reference lists of published articles was performed to identify relevant RCTs. Data were extracted for meta-analysis yielding pooled relative risks (RR) and 95% confidence intervals (CI). Sensitivity analyses by including studies with pseudo-randomization or unclear method of randomization were also performed (n=1141 patients in total). RESULTS: Four RCTs (n=587 patients) were eligible for inclusion. No statistically significant differences were present between patients who received a combination of progesterone and estrogen for luteal support when compared with those who received only progesterone, in terms of positive hCG rate (RR: 1.02, 95% CI: 0.87-1.19), clinical pregnancy rate (RR: 0.94, 95% CI: 0.78-1.13) and live birth rate (RR: 0.96, 95% CI: 0.77-1.21) per woman randomized. These results did not materially differ in the sensitivity analyses performed. CONCLUSIONS: The currently available evidence suggests that the addition of estrogen to progesterone for luteal phase support does not increase the probability of pregnancy in IVF. However, there is an obvious need for further RCTs that will assess, with more confidence, the effect of estrogen addition to progesterone during the luteal phase on the probability of pregnancy.

Abstract: OBJECTIVE: To examine the literature systematically in order to identify prospective comparative trials answering the following question: Is vitrification of human embryos associated with a higher postthawing survival rate as compared with slow freezing? DESIGN: Systematic review and meta-analysis. SETTING: University-based hospital. PATIENT(S): Not applicable. INTERVENTION(S): Vitrification versus slow freezing for cryopreservation of human embryos. MAIN OUTCOME MEASURE(S): Postthawing survival rate. RESULT(S): Four eligible studies were identified, three of which were randomized controlled trials. Overall, the current review summarizes information from 8,824 cryopreserved human cleavage stage embryos/blastocysts (vitrification: n = 7,482; slow freezing: n = 1,342). Survival rate of cleavage stage embryos was significantly higher after vitrification as compared with slow freezing (odds ratio 15.57, 95% confidence interval 3.68-65.82; random effects model). Postthawing survival rate of vitrified blastocysts was significantly higher compared with that observed with slow freezing (odds ratio 2.20, 95% confidence interval 1.53-3.16; fixed effects model). CONCLUSION(S): Vitrification appears to be associated with a significantly higher postthawing survival rate than slow freezing. Further prospective trials are necessary to confirm the above results and, in addition, allow the evaluation of the two cryopreservation methods in terms of pregnancy achievement.

Abstract: BACKGROUND: This study aimed to analyse the reproductive outcome of a large cohort of myotonic dystrophy type 1 (DM1) patients undergoing ICSI and PGD. The secondary outcome parameter of this study was ovarian response as a way to express gonadal function in female DM1 patients. METHODS: Prospective cohort study. Real and expected cumulative delivery rates are descriptive. The reproductive outcome per cycle was compared with that of a control group of patients with X-linked recessive disorders. The comparative analysis of ovarian stimulation parameters in the study group versus the control group was carried out using both bivariate (crude) and multivariate (linear regression) analysis. RESULTS: Between 1995 and 2005, 205 cycles of ICSI and PGD were carried out for DM1 in 78 couples. The real cumulative delivery rate (max 6 cycles) overall was 46%. The expected overall cumulative delivery rate was 72%. Multivariate analysis did not show a significant difference in total dose of gonadotrophins used for ovarian stimulation between Group A (in which the female partner was affected) and a control group. CONCLUSIONS: This study shows that ICSI and PGD for DM1 offer good reproductive outcome, both in cumulative terms and per treatment cycle. There is no evidence of impaired gonadal function in female DM1 patients.

Abstract: There is an ever increasing trend in reproductive medicine to reduce the intensity of ovarian stimulation for in vitro fertilization (IVF) and to restrict the number of embryos that are transferred into the uterine cavity. Recent findings suggest that the magnitude of ovarian stimulation affects the proportion of euploid embryos. As a result of the restriction in the number of embryos transferred, it becomes even more important to select the embryo with optimum implantational and developmental potential. Our aim was to asses the prevalence of numerical chromosomal abnormalities (aneuploidy) in unstimulated cycle IVF embryos. Thirty patients (mean age 31.4 years) underwent oocyte retrieval in a natural cycle without any form of ovarian stimulation, followed by intracytoplasmic sperm injection and Preimplantation genetic aneuploidy screening (PGS) for chromosomes X, Y, 13, 16, 18, 21 and 22. Out of 30 cycles, 21 oocytes were retrieved, 15 of which fertilized successfully. Eleven embryos developed sufficiently in order to undergo the PGS analysis, and four embryos proved to be aneuploid (36.4%; 95% CI: 10.9-69.2%). Six normal embryos were transferred in utero, resulting in three ongoing pregnancies. Two healthy girls were born and one patient miscarried. Numerical chromosomal abnormalities (aneuploidy) are present even in embryos of young women, and in the absence of ovarian stimulation.

Abstract: OBJECTIVE: To systematically review the literature to identify randomized controlled trials, which evaluate interventions aiming to improve the probability of pregnancy in poor responders undergoing in vitro fertilization (IVF). DESIGN: Systematic review and meta-analysis. SETTING: University-based hospital. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate. RESULT(S): Twenty-two eligible randomized controlled trials were identified that evaluated in total 15 interventions to increase pregnancy rates in poor responders. Based on limited evidence, the only interventions that appear to increase the probability of pregnancy were the addition of GH to ovarian stimulation (odds ratio for live birth: 5.22, confidence interval: 95% 1.09-24.99) and the performance of embryo transfer on day 2 compared with day 3 (ongoing pregnancy rate: 27.7% vs. 16.3%, respectively; difference: +11.4, 95% confidence interval: +1.6 to +21.0). CONCLUSION(S): Insufficient evidence exists to recommend most of the treatments proposed to improve pregnancy rates in poor responders. Currently, there is some evidence to suggest that addition of GH, as well as performing embryo transfer on day 2 versus day 3, appear to improve the probability of pregnancy.

Abstract: BACKGROUND: In IVF-ICSI cycles with single embryo transfer (SET), embryo selection for transfer is of crucial importance. The present study aimed to define which embryo parameters might be related to the implantation potential of advanced blastocysts. METHODS: Overall, in 203 cycles with SET, developmental characteristics of 93 implanted (group A) and 110 non-implanted (group B) advanced blastocysts of good quality were compared. The following developmental parameters were assessed in the two groups: normal fertilization, developmental stage on day 5, number of blastomeres on day 2 and on day 3, fragmentation rate on day 3, compaction on day 4 and cleavage pattern on day 2 and day 3. RESULTS: Expanded blastocysts compared to full blastocysts have higher implantation potential (56.5% vs. 29.3%, p < 0.05). In group B, a higher proportion of advanced blastocysts showed between 10% and 50% anucleated fragments on day 3 than in group A (23.6 vs 11.8, P = 0.03). Advanced blastocysts with >10-50% fragments on day 3 showed a significant lower implantation (29.7%) than those with < or = 10%fragments (49.4%, P = 0.03). All the other parameters analysed were comparable for the two groups. CONCLUSION: Developmental stage on day 5 and fragmentation rate on day 3 were related to the implantation potential of advanced blastocysts and should also be taken into account in the selection of the best advanced blastocyst for transfer.

Abstract: BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.

Abstract: BACKGROUND: The Belgian legislation imposes single embryo transfer (SET) on women of <36 years in their first treatment cycle to avoid multiple pregnancies. The aim of this study is to assess the impact of this legislation on the outcome of preimplantation genetic diagnosis (PGD) for inherited diseases in young women undergoing SET. METHODS: A retrospective analysis of PGD cycles for monogenic disorders and translocations in women <36 years on their first treatment cycle. Two groups of patients were defined according to the implementation of the Belgian legislation: (i) double embryo transfer (DET), January 2001-June 2003 (ii) SET, July 2003-June 2005. The primary and secondary outcome measures were delivery per embryo transfer and multiple pregnancy rates, respectively. A subgroup analysis for monogenic disorders and translocations was performed. RESULTS: 62 cycles were included in the DET group and 73 cycles in the SET group. The mean age, number of cumulus-oocyte complexes, number of fertilized oocytes, number of biopsied and cryopreserved embryos were comparable between both groups. There was no significant difference in the delivery rates between the DET and the SET groups (33.9% versus 27.4%, respectively). Multiple pregnancies were avoided when SET was performed. When monogenic disorders and chromosomal translocations were separately evaluated, no significant difference in the delivery rate after SET was observed. CONCLUSIONS: The implementation of a SET policy in young women undergoing PGD for monogenic disorders and translocations enables a significant reduction of multiple pregnancies without significantly affecting the delivery rate.

Abstract: OBJECTIVE: To explore luteal phase hormone profiles in patients stimulated with recombinant FSH and GnRH antagonist for IVF under two different modes of luteal support: P and P with E(2). DESIGN: Prospective randomized study. SETTING: Patients in an academic reproductive medicine unit. PATIENT(S): One hundred and three patients undergoing ovarian stimulation with a fixed dose of 200 IU recombinant FSH and GnRH antagonist. INTERVENTION(S): Patients were randomized to receive luteal phase supplementation, either P vaginally (n = 49) or P and 4 mg E(2) orally (n = 54). MAIN OUTCOME MEASURE(S): Hormonal assessment during the luteal phase on days 1, 4, 7, and 10 after the administration of hCG. RESULT(S): Hormone levels did not differ during the luteal phase between the two groups with the exception of E(2) concentration on day 10 after hCG, which was significantly higher in the E(2)-supplemented group compared with the P group (median 760 pg/mL, range 2,496 vs. median 589.50 pg/mL, range 2,098). CONCLUSION(S): Addition of 4 mg E(2) for luteal support after stimulation with recombinant FSH and GnRH antagonist does not alter significantly the endocrine profile of the luteal phase until day 7 after hCG. At day 10 after hCG, the E(2) levels are significantly higher in the E(2)-supplemented group.

Abstract: The role of progesterone elevation on in vitro fertilization (IVF) outcome has remained a debatable issue for several years. The aim of this systematic review and meta-analysis was to evaluate whether progesterone elevation on the day of human chorionic gonadotrophin (hCG) administration is associated with the probability of pregnancy. Eligible studies were considered those in which patients did not participate more than once. A literature search in MEDLINE, EMBASE and CENTRAL identified 12 eligible studies, 10 of which were retrospective. The majority (n = 10) of these studies did not detect a statistically significant association between progesterone elevation and the probability of pregnancy. Meta-analysis was performed only for the studies (n = 5) that provided data on clinical pregnancy per patient reaching hCG administration for final oocyte maturation. No statistically significant association between progesterone elevation and the probability of clinical pregnancy was detected (Odds ratio: 0.75, 95% confidence interval 0.53-1.06; P = 0.10). This finding persisted in the sensitivity analyses performed, which excluded the studies that did not report clearly that measurement of progesterone did not affect patients' management and those that did not report definition of clinical pregnancy. In addition, subgroup analyses were conducted on the basis of type of gonadotrophin-releasing hormone GnRH analogue used and on the value of serum threshold used to classify patients in those with or without progesterone elevation. These analyses, however, did not materially change the results obtained. In conclusion, the best available evidence does not support an association between progesterone elevation on the day of hCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF.

Abstract: Four hundred eighty-two patients undergoing single ET with GnRH-antagonist/recFSH protocol were analyzed. The incidence of premature luteinization (P above 1.5 ng/mL on the day of hCG administration) was 18.2%. Even modest rises of P in the follicular phase have detrimental effect on the implantation potential of a good-quality cleavage stage embryo. On the contrary, premature luteinization in the blastocyst subgroup had no effect on the pregnancy outcome.

Abstract: OBJECTIVE: To evaluate the effect of different human chorionic gonadotropin (hCG) doses on the ongoing pregnancy rates in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary university referral center. PATIENT(S): Eighty PCOS patients. INTERVENTION(S): Patients were randomized to receive 10,000 IU (n = 28), 5000 IU (n = 26), or 2500 IU (n = 26) of hCG for triggering final oocyte maturation as soon as >or=3 or more follicles of 17 mm or larger were present at ultrasound. Patients were stimulated with recombinant follicle stimulating hormone (FSH) and daily gonadotropin-releasing hormone (GnRH) antagonist, starting on day 6 of stimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, fertilization rates. RESULT(S): The median fertilization rates were 52.8%, 65.4%, and 55.6% after administration of 10,000 IU, 5000 IU and 2500 IU, respectively. The ongoing pregnancy rates per PCOS patient receiving hCG were 26.9% (7 of 26), 30.8% (8 of 26) and 34.8% (8 of 23), respectively. CONCLUSION(S): A decrease in the dose of hCG used to trigger final oocyte maturation does not appear to affect adversely the probability of pregnancy in PCOS patients treated by IVF using GnRH antagonists and recombinant FSH, and further testing in future larger-scale trials is recommended.

Abstract: Stimulated IVF cycles are associated with luteal phase defect. In order to overcome this, different doses, durations and types of luteal phase support (LPS) have been evaluated. There is still no agreement regarding the optimal supplementation scheme. The aim of this paper is to assess the past and the current clinical practices of luteal supplementation in IVF. The databases of Medline and PubMed were searched to identify relevant publications. LPS with human chorionic gonadotrophin (hCG) [n=262, odds ratio (OR) 2.72 (95%), confidence interval (CI) 1.56-4.90, P<0.05] or progesterone (n=260, OR 1.57 CI 1.13, 2.17, P<0.05) results in an increased pregnancy rate compared with placebo, however, hCG is associated with increased risk of ovarian hyperstimulation syndrome. Natural micronized progesterone is not efficient if taken orally. The data on oral dydrogesterone are still conflicting. Vaginal and intra muscular progesterone have comparable outcomes. The addition of estradiol (E2) seems to be beneficial in long GnRH agonist protocol (implantation rate 39.6% with E2 compared with no E2; P<0.05) but not in the short GnRH agonist and GnRH antagonist protocol. Despite the early promising results, it is too early to recommend the use of GnRH agonist in LPS. LPS should cease on the day of positive HCG. Since the cause of luteal phase defect in IVF appears to be related to the supraphysiological levels of steroids, milder stimulation protocols should be advocated in order to eventually overcome the luteal phase defect.

Abstract: The aim of this systematic review and meta-analysis was to assess whether the addition of recombinant luteinizing hormone (LH) increases live birth rate, among patients treated with follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) analogues for in vitro fertilization (IVF). Eligible studies were randomized controlled trials (RCTs) answering the research question that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared, regarding baseline demographic characteristics, gonadotrophin stimulation protocol, number of embryos transferred and luteal phase support administered. A literature search identified seven RCTs (701 patients) that provided the information of interest, among which five reported agonist and two antagonist cycles. The reported outcome measure, clinical pregnancy, was converted to live birth using published data in one study. No significant difference in the probability of live birth was present with or without rLH addition to FSH (odds ratio [OR]: 0.92, 95% confidence interval (CI): 0.65-1.31; P = 0.65). This finding remained stable in subgroup analyses that ordered the studies by dose of rLH added, the type of analogue used to inhibit premature LH surge, the time rLH was added during the follicular phase, the age of patients analysed, the presence of allocation concealment and by the way the information on live birth was retrieved. In conclusion, the available evidence does not support the hypothesis that the addition of recombinant LH increases the live birth rate in patients treated with FSH and GnRH analogues for IVF.

Abstract:

Abstract: OBJECTIVE: To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation in the collecting cycle with GnRH-antagonist. DESIGN: Prospective, observational, multicentric clinical study. SETTING: Tertiary university-affiliated IVF centers. PATIENT(S): Patients under observation previously had been recruited into two concurrently performed, independent, randomized controlled trials (comparing hCG with GnRH-agonist for triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in normal responder patients) encompassing a total of 228 participants. Surplus embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients after hCG administration and 32 patients after GnRH-agonist administration on the basis of patient choice, pronuclear/embryo availability, and local laws. INTERVENTION(S): Transfer of frozen-thawed embryos. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Thirty-one and 23 patients after administration of hCG and GnRH-agonist, respectively, started a frozen-embryo replacement cycle by September 2005, with 25 and 16 patients eventually undergoing at least one frozen-thawed ET. Live birth rate per ET was 18.5% (95% confidence interval [CI], 8.2-36.7) and 30.0% (95% CI, 14.5-51.9) after hCG and GnRH-agonist triggering, respectively. Cumulative live birth rate per patient starting a frozen-embryo replacement cycle was 16.1% (95% CI, 7.1-32.6) and 26.1% (95% CI, 12.5-46.5) for hCG and GnRH-agonist, respectively. CONCLUSION(S): The likelihood of live birth in frozen-embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation does not appear to be impaired.

Abstract: BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.

Abstract: BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.

Abstract: The aim of this systematic review was to evaluate, among women with normal ovulation or World Health Organization (WHO) II oligoanovulation who undergo ovarian stimulation for IVF using GnRH analogues, whether endogenous LH levels predict the likelihood of ongoing pregnancy beyond 12 weeks. A literature search identified six studies that answered the research question, among which two were prospective studies (one in GnRH agonist and one in GnRH antagonist cycles). None of the retrospective studies suggest that low endogenous LH levels are associated with a significantly decreased probability of ongoing pregnancy beyond 12 weeks in such patients. In the two prospective studies high endogenous LH levels during down-regulation were associated with a decreased probability of ongoing pregnancy beyond 12 weeks. Until further prospective studies modify the existing evidence summarized here, an adverse effect of low endogenous LH levels on the probability of ongoing pregnancy beyond 12 weeks is not a sensible rationale for LH supplementation during ovarian stimulation for IVF using GnRH analogues.

Abstract: OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS) in a large series of GnRH antagonist-stimulated cycles and to assess the predictive value of E2 and the number of follicles on the day of hCG administration. DESIGN: Prospective cohort study of women undergoing IVF treatment with a GnRH antagonist protocol over a 2-year period. SETTING: Tertiary university hospital. PATIENT(S): One thousand eight hundred one patients who underwent 2,524 cycles. INTERVENTION(S): Multifollicular ovarian stimulation with recombinant FSH and GnRH antagonist for IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Incidence of OHSS in GnRH antagonist cycles, predictive value of E2, and number of follicles on the day of hCG for OHSS occurrence. RESULT(S): Fifty-three patients were hospitalized because of OHSS (2.1%; 95% confidence interval [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8), whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3). Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and more often were related to a multiple pregnancy (40% vs. 0). Receiver operating characteristic curve analysis for several E2 concentrations and number of follicles with a diameter of > or =11 mm revealed that the predictive value of the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity) was statistically significantly superior to the optimal threshold of 2,560 ng/L for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients at risk for OHSS. Considering that severe OHSS represents the most clinically significant pattern, the combination of a threshold of > or =18 follicles and/or E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high as 84% for the severe OHSS cases. CONCLUSION(S): Clinically significant OHSS still remains a limitation of multifollicular ovarian stimulation for IVF even with the use of GnRH antagonist protocols. The number of follicles can discriminate the patients who are at risk for developing OHSS, whereas E2 concentrations are less reliable for the purpose of prediction. There is more than ever an urgent need for alternative final oocyte maturation-triggering medication.

Abstract: BACKGROUND: An increased incidence of aneuploid embryos has been recently described from azoospermic men. The aim of this study was to assess if embryo selection on day 5, based on morphological criteria, would be different from the selection based on PGD for aneuploidy screening (AS) in couples undergoing ICSI for male azoospermia. METHODS: Sixty-two cycles of testicular sperm extraction (TESE)-ICSI with PGD-AS were included in the analysis. Two embryologists, blinded to the PGD-AS results, retrospectively reviewed the available embryology data from day 5 embryos and selected one, two or three embryos to be transferred. These results were compared with the selected embryos based on PGD-AS. RESULTS: A total of 39 cycles from non-obstructive azoospermia (NOA) and 23 cycles from obstructive azoospermia (OA) were retrospectively analysed. If single embryo transfer (SET) had been performed, in 64.8% of the NOA cycles and 54.5% of the OA cycles, no difference in embryo choice would have occurred compared to PGD-AS and in 10.8 and 36.6% of the cycles, respectively, an aneuploid embryo would have been chosen. If double ET (DET) had been performed, in 72.9% of the NOA cycles and 86.5% of the OA cycles, no difference in embryo choice would have occurred compared to PGD-AS and in 2.7 and 4.5% of the cycles, respectively, an aneuploid embryo would have been chosen. If triple ET (TET) had been performed, the outcome would have been the same as for DET. DISCUSSION: Our results suggest that under the terms of an SET policy, the performance of PGD-AS in azoospermia would result in a higher chance of success, as the possibility of selecting a euploid embryo is enhanced.

Abstract: This prospective randomized pilot study was aimed at investigating the effect of the novel addition of aromatase inhibitors to an ovarian stimulation protocol for IVF or intracytoplasmic sperm injection, on endocrine parameters including serum androgen, oestrogen, progesterone, LH and FSH concentrations. The patients were randomized to receiving letrozole (group A; n = 10), versus no letrozole (group B; n = 10) in an ovarian stimulation protocol with recombinant FSH 150 IU/day starting on day 2 of the cycle, and gonadotrophin-releasing hormone antagonist 0.25 mg/day starting on day 6 of the cycle. Median LH concentrations were significantly higher (P < 0.01) in group A versus group B during letrozole administration. Median serum oestradiol concentrations were lower in group A versus group B, and median serum FSH, testosterone and androstenedione concentrations were higher in group A versus group B, throughout the follicular phase, without reaching significance. Median endometrial thickness was significantly higher (P < 0.05) in group A versus group B on the day of human chorionic gonadotrophin administration. Pregnancies were achieved. This pilot study supports the idea that aromatase inhibitors can contribute to normal potential of implantation and follicular response, without having negative anti-oestrogenic effects.

Abstract: The current study aimed to investigate whether single day-3 embryo transfer (SET) results in higher early pregnancy loss (EPL) than single blastocyst transfer (SBET). A total of 896 patients underwent 1103 IVF cycles with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. In 603 cycles (D3 group) a single embryo on day 3 of the embryo culture was transferred, whereas in the remaining 500 cycles a single blastocyst was transferred on day 5 (D5 group). Multifollicular ovarian stimulation was performed with a GnRH antagonist protocol starting on day 6. SET resulted in 209 pregnancies (34.7%), compared with 221 pregnancies (44.2%) for SBET. Early pregnancy loss rate was significantly higher with SET compared with SBET (26.8% versus 17.2%, P = 0.017) and ongoing implantation rate was also significantly higher with day 5 compared with day-3 embryo transfer (OR:1.68, 95% confidence interval:1.31-2.18). Sub-optimal embryo selection for transfer on day 3, in addition to asynchronization between altered endometrium and early exposure of cleavage-stage embryos, might explain the above difference. Nevertheless, the higher implantation potential of the blastocyst questions the rationale behind performing single embryo transfer on day 3 of embryo culture in women under 36 years old.

Abstract: BACKGROUND: The role of progesterone for luteal support in stimulated cycles for IVF is well established. However, controversy still surrounds the benefit of additional supplementation with estradiol (E2) in GnRH agonist (GnRHa) cycles, while no such data are available for GnRH antagonists. The aim of this randomized controlled trial (RCT) was to compare ongoing pregnancy rates in patients stimulated with recombinant FSH (rFSH) and GnRH antagonist for IVF, who received micronized progesterone for luteal phase supplementation, with or without the addition of E2. METHODS: Two hundred and one patients underwent ovarian stimulation with a fixed dose of 200 IU rFSH and GnRH antagonist. Patients were randomized to receive, for luteal phase supplementation, either 600 mg of micronized progesterone vaginally (n=100, progesterone group) or 600 mg of micronized progesterone and 4 mg of E2 valerate orally (n=101, progesterone/E2 group). The main outcome measure was ongoing pregnancy at 12 weeks per patient randomized. RESULTS: Demographics, stimulation parameters and embryological data were comparable for the two groups compared. Twenty-six ongoing pregnancies were achieved in the progesterone (26%) and 30 in the progesterone/E2 group (29.7%). (Difference: 3.7 and 95%, CI: -15.8 to 8.6%). CONCLUSION: It appears that the addition of E2 to progesterone in the luteal phase after stimulation with rFSH and GnRH antagonist does not enhance the probability of pregnancy.

Abstract: BACKGROUND: Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age. We designed a prospective, randomized, controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage (day 3) embryo and those undergoing transfer of a single blastocyst-stage (day 5) embryo. METHODS: We studied 351 infertile women under 36 years of age who were randomly assigned to undergo transfer of either a single cleavage-stage embryo (176 patients) or a single blastocyst-stage embryo (175 patients). Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone. RESULTS: The study was terminated early after a prespecified interim analysis (which included 50 percent of the planned number of patients) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo (P=0.02). The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo (32.0 percent vs. 21.6 percent; relative risk, 1.48; 95 percent confidence interval, 1.04 to 2.11). Two multiple births occurred, both of monozygotic twins, both of which were in the group undergoing transfer of a single cleavage-stage embryo. CONCLUSIONS: These findings support the transfer of a single blastocyst-stage (day 5) embryo in infertile women under 36 years of age.

Abstract: PURPOSE OF REVIEW: During folliculogenesis the primordial follicle undergoes several steps of maturation in order to develop into a preovulatory follicle. The exact role of estrogen during this process has not yet been fully assessed. RECENT FINDINGS: Estrogen appears to regulate cyclic gonadotropin release via its action on estrogen receptor alpha in the hypothalamus/hypophysis axis and to enhance folliculogenesis through its actions via estrogen receptor beta in the ovary. In addition, a role of estrogen during the very early stages of folliculogenesis is possible. However, it is likely that oocyte quality and developmental potential are not estrogen dependent. This might explain the lack of association between estrogen and in-vitro fertilization outcome in humans. SUMMARY: The advent of knockout mice models has enhanced our understanding of the role of estrogen during folliculogenesis. Existing data suggest that estrogen might be involved in the very early steps of this process, but its role in sustaining ovulation is mainly central.

Abstract: Gonadotrophin-releasing hormone agonist (GnRHa) administration from the mid-luteal phase onwards is considered the gold standard of ovarian stimulation for IVF treatment. It might, however, coincide with an implanting spontaneous pregnancy. Concerns have therefore been raised with regard to the evolution of the resulting pregnancies and long-term outcome of the children born. The current case report describes the achievement of three pregnancies in the same patient during luteal administration of GnRHa. One pregnancy ended in spontaneous abortion and the other two resulted in the delivery of two female infants. The children have so far been followed for 3.5 and 7 years. The physical examination of both children was unremarkable. However, the older child has recently been diagnosed with attention deficit hyperactivity disorder and dyslexia.

Abstract: BACKGROUND: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). METHODS: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). RESULTS: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. DISCUSSION: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.

Abstract: BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early onset) or a late pattern (late onset). This observational study was designed to identify whether the onset pattern of OHSS is associated with the occurrence of pregnancy and the early pregnancy outcome. METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized for OHSS after IVF/ICSI treatment and were included in the study. The setting was the Dutch-speaking Brussels Free University Hospital, between June 2000 and September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (P < 0.05). Although in the early group there initially was a 41.5% positive HCG rate per cycle, the clinical pregnancy rate fell to 28.3% as a result of a significantly (P < 0.05) increased preclinical pregnancy loss rate compared with the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple pregnancy rates were high in both groups (40 and 45.5%, respectively), but only in the late group did the incidence reach significance compared with the non-OHSS population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of follicles on the day of HCG were significantly higher in the early OHSS group. However, there was no difference in estradiol values on the day of hospital admittance between the two groups. In addition, the number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS than the estradiol values (87% of the severe cases had > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.

Abstract: BACKGROUND: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. METHODS: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as > or =3 follicles > or =17 mm were present on ultrasound (early-hCG group, n = 5) or 2 days after this criterion was met (late-hCG group, n = 5). RESULTS: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). CONCLUSIONS: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

Abstract: Infertility affects approximately 15% of couples of reproductive age. In assisted reproductive technology (ART), medications play a crucial role in stimulating ovaries to produce several oocytes and prepare the endometrium to be receptive after replacing one or more embryos into the uterine cavity. The availability of recombinant human follicle stimulating hormone, luteinising hormone and human chorionic gonadotrophin; of gonadotrophin-releasing hormone (GnRH) agonists and antagonists; and of luteal supplementation with progesterone have allowed the tailoring of several stimulation schemes, which have enhanced the pregnancy outcome after ART treatment. However, the remaining risk of ovarian hyperstimulation syndrome, the still low implantation rates, the unacceptably high rates of multiple pregnancies and the daily parenteral administration of medications do not constitute the features of a patient-friendly procedure. Therefore, a number of molecules with gonadotrophin-like activity, inhibition of GnRH receptor ability, or endometrium receptivity enhancement properties are currently under active investigation. Orally bioactive therapeutic preparations, in particular, may revolutionize in vitro fertilisation (IVF) treatment in the near future. Nevertheless, the implementation of mild ovarian stimulation protocols with single embryo transfer policy and further development of oocyte in vitro maturation techniques may lead to a less drug orientated IVF treatment.

Abstract: INTRODUCTION: In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. METHODS: Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. RESULTS: Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). CONCLUSIONS: A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.

Abstract: The current case report describes the development and medical treatment of an aggressive pelvic endometrioma in a post-menopausal patient, who had undergone abdominal hysterectomy and salpingo-oophorectomy a decade earlier. The patient was referred to the authors' centre because of right-sided sciatic pain. Three months before her admission she was hospitalized elsewhere due to subacute bowel obstruction. She was operated on and a resection of a part of sigmoid colon and an endometrioma, which was the cause of the subobstruction, was carried out. During the clinical investigation for the right-sided sciatic pain, an intrapelvic mass was found, which was compressing the lumbo-sacral plexus mimicking sciatica. The diagnosis of recurrent endometrioma was confirmed by a computerized tomography-guided biopsy and the decision was made to treat it with an aromatase inhibitor (letrozole). Eighteen months later, the endometrioma was almost completely regressed and the patient was free of symptoms. Medical management of recurrent post-menopausal endometriosis with aromatase inhibitors seems to be an effective alternative treatment to surgery.

Abstract: The development of immature oocyte collection techniques for in-vitro maturation (IVM), combined with novel culture techniques, opens new possibilities for assisted reproductive technology. Optimization of clinical management of IVM cycles will enhance pregnancy outcome, so that IVM might become an effective alternative assisted reproduction treatment for infertile patients irrespective of the cause of infertility. Parameters such as age and baseline antral follicular count are predictive of outcome and should be used as selection criteria for IVM treatment. Women with polycystic ovary disease and normo-ovulatory patients at risk of developing ovarian hyperstimulation syndrome might benefit from earlier retrieval of oocytes followed by IVM and embryo transfer. HCG priming before oocyte retrieval seems beneficial in terms of oocyte yield and maturational competence, and may increase the harvest of mature oocytes and lead to better endometrial synchronization with the developing embryo. The timing of aspiration may be crucial in IVM and selection criteria for follicle size at aspiration need defining prospectively for infertility type. Finer calibre aspiration needles and low aspiration pressure yield more oocytes. A combination of natural cycle IVF with IVM is a promising, mild and inexpensive assisted reproduction treatment, widely accessible the infertile population.

Abstract: BACKGROUND: There is no agreement about the frequency of chromosomal abnormalities (CAs) in the female partner of an infertile couple and therefore there is no evidence base for determining whether karyotype analysis is mandatory before the initiation of infertility treatment. The aim of this prospective study was to estimate the prevalence of karyotype abnormalities in normovulatory women attending an infertility clinic and compare it to that known to be present in the newborn female population. METHODS: Cytogenetic testing was performed in 1206 women with normal ovulatory cycle seeking infertility treatment. At least 15 GTG-banded metaphases were analysed in each case. In the case of a structural abnormality, fluorescent in situ hybridization (FISH) analysis and high resolution banding (HRB) were performed on a new blood sample to elucidate the aberration. When mosaicism was suspected, the number of analysed metaphases was increased to a total of 115 and an additional analysis of 200 metaphases was done on a second blood sample. RESULTS: A chromosomal abnormality was demonstrated in 0.58% (95% CI: 0.28-1.19) of cases which did not differ significantly from that reported in female newborns (0.79%; 95% CI: 0.68-0.94). Balanced reciprocal translocation was observed in 0.4% of patients (n = 5), paracentric inversion of chromosome X in 0.08% (n = 1) and gonosomal mosaicism in 0.08% (n = 1). However, chromosomal aberrations were less common among females with primary infertility compared to those with secondary infertility (0.25 versus 1.25%, P = 0.04). CONCLUSIONS: The present study suggests that routine cytogenetic analysis cannot be advocated in normovulatory infertile women. Nevertheless, the relatively higher frequency of abnormal karyotypes in women with secondary infertility indicates that this subgroup of patients might benefit from a routine karyotype analysis.

Abstract: Normal menopause is associated with vascular endothelial dysfunction, an early stage of atherosclerosis. The effect of premature ovarian failure (or premature menopause) on endothelial function in young women is unknown. Endothelial function was assessed in 18 women with premature ovarian failure before and after 6 months of hormone therapy and was compared with the endothelial function of 20 age- and body mass index-matched premenopausal women. Brachial artery diameter was measured both during hyperemia (an index of endothelium-dependent vasodilation) and in response to glyceryl trinitrate (an index of endothelium-independent vaso-dilation). Flow-mediated dilation was significantly lower in women with premature ovarian failure at baseline (increase in brachial artery diameter during hyperemia by 3.06 +/- 4.33%) than in control women (increase by 8.84 +/- 2.15%; P < 0.0005). Glyceryl trinitrate-induced vasodilation did not differ between the groups. After hormone therapy for 6 months, flow-mediated dilation was improved in women with premature ovarian failure, increasing by more than 2-fold (7.41 +/- 3.86%; P < 0.005 compared with pretreatment) and reaching normal values (P not significant compared with control women). Glyceryl trinitrate-induced vasodilation did not change after treatment in women with premature ovarian failure. Young women with premature ovarian failure have significant vascular endothelial dysfunction. Early onset of endothelial dysfunction associated with sex steroid deficiency may contribute to the increased risk of cardiovascular disease and mortality in young women with premature ovarian failure. Hormone therapy restores endothelial function within 6 months of treatment.

Abstract: BACKGROUND: The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation. MATERIAL AND METHODS: One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed. The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours. Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome. RESULTS: The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group (11.9 h vs. 15.5 h, p < 0.001). With misoprostol, more women delivered within 12 hours (57.5% vs. 32.5%, p < 0.01) and 24 hours (98.7% vs. 91.4%, p < 0.05), spontaneous rupture of the membranes occurred more frequently (38.8% vs. 20.5%, p < 0.05), there was less need for oxytocin augmentation (65.8% vs. 81.5%, p < 0.05) and fewer additional doses were required (7.5% vs. 22%, p < 0.05). Although not statistically significant, a lower Caesarean section (CS) rate was observed with misoprostol (7.5% vs. 13.3%, p > 0.05) but with the disadvantage of higher abnormal fetal heart rate (FHR) tracings (22.5% vs. 12%, p > 0.05). From the misoprostol group more neonates were admitted to the intensive neonatal unit, than from the dinoprostone group (13.5% vs. 4.8%, p > 0.05). One woman had an unexplained stillbirth following the administration of one dose of dinoprostone. CONCLUSIONS: Vaginal misoprostol, compared with dinoprostone in the regimens used, is more effective in elective inductions of labor beyond 40 weeks of gestation. Nevertheless, this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit, indicating that the faster approach is not necessarily the better approach to childbirth.

Abstract: Trisomy 18 is the second most common multisystem malformation syndrome. We present here a case of a fetus with trisomy 18, in which upper limb reduction was detected prenatally, as an isolated defect, at 17 weeks of gestation. The pregnancy was terminated by vaginal administration of misoprostol, and postmortem examination confirmed the ultrasound findings, including bilateral upper limb reduction with radial aplasia, absent first metacarpal and thumb and ventrally hyperflexed hands. This case demonstrates the need for thorough ultrasound evaluation of the fetal hands, as early as possible, because upper limb deformities can be the only abnormality of trisomy 18.

Abstract: BACKGROUND: Misoprostol is a prostaglandin E(1) analogue that has been used for medical abortion. We conducted this prospective study to compare the efficacy of vaginal misoprostol for abortion in women at a gestational age of <42 days and in women at a gestational age of 42-56 days. METHODS: A total of 160 women seeking medical termination of a pregnancy of <56 days were enrolled in the study. Medical termination was performed using 800 micro g of vaginal misoprostol, repeated every 24 h for a maximum of three doses. RESULTS: The overall complete abortion rate was 91.3%. In group A (gestation <42 days) complete abortion occurred in 96.3% of women, whereas in group B (gestation = 42-56 days) complete abortion occurred in 86.3% of women (P < 0.025). The two groups did not differ significantly with respect to side-effects (incidence of pain, bleeding, nausea, diarrhoea, fever and headache). Women who had aborted successfully were significantly more satisfied with the method compared with women who did not (P < 0.001). CONCLUSIONS: The vaginal misoprostol-alone regimen is highly effective for women seeking medical abortion of pregnancies of <or=56 days. However, better efficacy may be achieved at a gestational age of <42 days.

Abstract: Bacterial vaginosis (BV) is a polymicrobial infection of the vagina and should not be considered an exclusively sexually transmitted disease. We describe the case of a 17-year-old female virgin adolescent with recurrent malodorous vaginal discharge for 6 months. Before referral to us she had been treated unsuccessfully with conservative treatment options. Our investigation revealed Gardnerella vaginalis as the responsible factor for the vaginal infection. Because metronidazole treatment had failed as monotherapy, a new method was applied. Repeated vaginal washings with 3% H(2)O(2), 15% NaCl and 10% providone iodine were initiated. At the end of each washing, vaginal walls were thoroughly cleaned up with a small gauze. After 10 days of treatment the odor and the vaginal discharge had ceased and 12 months later no relapse had occurred. It seems to be reasonable to use this kind of treatment in recurrent BV.