Down-regulation Protocol Research Articles

WITHDRAWN: Human menopausal gonadotropin versus recombinant follicle stimulation hormone for ovarian stimulation in assisted reproductive cycles.

hMG and recombinant FSH, have both been used successfully for controlled ovarian hyperstimulation in in vitro fertilization and embryo transfer (IVF-ET). To compare the effectiveness of hMG with rFSH in ovarian stimulation protocols in IVF or ICSI treatment cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 3rd Jan 2002), PubMed, MEDLINE, Web of Science (all searched 1985 to May 15 2002), and reference lists of articles. We also contacted manufacturers and researchers in the field. Randomised trials comparing hMG with rFSH for ovarian stimulation in IVF or ICSI treatment for treatment of infertility in normogonadotrophic women. The main outcome measure was ongoing pregnancy/live birth per woman.Secondary outcomes included total gonadotrophin dose used, cancellation, number of oocytes retrieved, implantation, clinical pregnancy per woman, multiple pregnancy, spontaneous abortion and ovarian hyperstimulation syndrome. Peto odds ratios (OR) for hMG relative to rFSH were calculated after testing for homogeneity of treatment effect across all trials. Analyses were performed separately for the three different GnRHa protocols used: (1) without GnRHa down-regulation, (2) with GnRHa down-regulation using a short protocol and (3) with GnRHa down-regulation using a long protocol. Eight trials that met the inclusion criteria could be identified. One trial did not use down-regulation, one trial used a short protocol and six trials used a long down-regulation protocol. In the one trial with non-down-regulated women and in the one trial that used a short down-regulation protocol there was no evidence of a difference between hMG and rFSH in any clinical outcome. Data of four truly randomised trials in women down-regulated using a long protocol could be pooled. There was no evidence of a difference between hMG and rFSH in ongoing pregnancy/live birth per woman (OR 1.27; 95% CI 0.98 to 1.64). Furthermore there was no clear difference on any of the secondary outcomes, although the clinical pregnancy rate per woman was of borderline significance in favour of hMG (summary OR 1.28; 95% CI 1.00 to 1.64). The other secondary outcomes were comparable for both gonadotrophins. For all three GnRHa protocols analysed there is insufficient evidence of a difference between hMG and rFSH on ongoing pregnancy or live birth. More large randomised trials are needed to estimate the difference between hMG and rFSH more precisely. Such trials should preferably (1) use a consistent long GnRHa protocol and (2) use a fixed dose of gonadotrophin such to prevent potentially subjective decisions of the clinician in dosing and (3) take live birth as primary endpoint. At this moment in time however, in prescribing gonadotrophins for ovarian hyperstimulation in IVF one should use the least expensive medication.

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-β variant: v-βLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000-3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-βLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B ( P < 0.05) and C ( P < 0.001). Group A had a significantly lower ( P < 0.05) number of oocytes retrieved (7.3 ± 1.5, 11.7 ± 2.4 and 14.7 ± 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-βLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-βLH is more frequent in women with ovarian resistance to rhFSH.

Association of basal serum testosterone levels with ovarian response and in vitro fertilization outcome

BackgroundTo evaluate basal testosterone (T) levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF) outcome.MethodWe analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS) or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L) (n = 187); Group 2: patients with normal ovarian reserve (basal FSH < = 10 IU/L) (n = 1073). We studied the association of basal T levels with ovarian response and IVF outcome in the two groups. Long luteal down-regulation protocol was used in all patients, that is, the gonadotropin releasing hormone agonist was administered in the midluteal phase of the previous cycle and use of recombinant FSH was started when satisfactory pituitary desensitization was achieved.ResultsBasal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm) on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups.ConclusionIn women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.

Controlled ovarian hyperstimulation for low responders in in vitro fertilization/intracytoplasmic sperm injection: a low-dose flare protocol

In this retrospective study of 652 anticipated low response women, the overall clinical outcomes (live birth rate and clinical pregnancy rate [PR]) of low-dose flare (LDF) protocol appeared lower than those of conventional down-regulation (DR) (LDF: 15.1% vs. DR: 20.6% and LDF: 10.3% vs. DR: 17.4%, respectively). The findings that LDF protocol improved the clinical outcome in older women, or when LDF followed an unsuccessful IVF/intracytoplasmic sperm injection (ICSI) cycle with DR (LDF: 19.4% vs. DR: 9.76% and LDF: 13.9% vs. DR: 4.2% respectively), need further evaluation through randomized trials.

The effect of cabergoline on folicular microenviroment profile in patients with high risk of OHSS

OBJECTIVE: Dopamine agonists have been proposed as a prophylactic treatment for ovarian hyperstimulation syndrome (OHSS) in women at high risk in IVF/ICSI treatment cycles, however the possible mechanism of action has not been known. The main aim of this study is to investigate the effect cabergoline on the follicular fluid hormone levels. DESIGN: In this prospective age and body mass index (BMI) matched case control study, a total of 41 women with PCOS diagnosed and treated for primary infertility at the IVF center were included. Main inclusion criteria were development of more than 14 leading follicles larger than 10 mm and serum estradiol more than 3000 pg/ml at the end of ovulation induction with long downregulation protocol. The patients in study (15 patients) was administered cabergoline (started on day of HCG) for prevention of OHSS, the patients (n=26) in the control group had manipulation for prevention of OHSS and age-, BMI-matched with the study group. Follicular fluid samples were collected in whole group, on day of oocyte pick-up. MATERIALS AND METHODS: Four markers markers (Antimullerian hormone (AMH), Inhibin B, Hepatocyte growth factor (HGF), Insulin like growth factor-1 (IGF-1) with commercially available ELISA kits were studied in follicular fluid samples. Follicular fluid hormones concentrations were compared between the study and control groups using a Mann–Whitney U test. RESULTS: In the study group follicular fluid AMH (2.96 ± 1.27 vs. 1.91 ± 0.64, p=0.005), Inhibin B (1339.47 ± 198.56 vs. 1200.09 ± 133.64, p=0.021), HGF (5623.21 ± 2411.09 vs. 3787.42 ± 2269.89, p=0.021) and IGF-1 (298.60 ± 37.80 vs. 219.90 ± 71.40, p<0.001) concentrations were significantly decreased compared with control group. No cases of OHSS was observed in study group ,while the OHSS rate was 15/26 in control group. There was no statistically significant difference in clinical pregnancy rates between two groups. CONCLUSION: Cabergolin prevent OHSS in high risk patients by disrupting folliculer fluid hormone microenviroment.

The use of anti-Müllerian hormone and antral follicle count to predict the potential of oocytes and embryos

Objective To investigate whether anti-Müllerian hormone (AMH) is better than antral follicle count (AFC) in predicting oocyte yield and embryo quality after controlled ovarian hyperstimulation for in vitro fertilization (IVF). Study design This is a prospective observational study involving 162 women (<40 years old) undergoing their first IVF cycle at an IVF unit within a university hospital. AMH and AFC measurements were made on day 3 of the cycle within 3 months of starting ovarian stimulation. A standard long down-regulation protocol using gonadotrophin releasing hormone agonist and recombinant follicle stimulating hormone was used. A maximum of two embryos were transferred on day 2 or 3 following oocyte retrieval. The primary outcome was the number of good quality embryos available for transfer and freezing. Embryos were graded according to the number of blastomeres, the difference in blastomere size and the degree of fragmentation, into grades 1–4. Secondary outcomes included the number of oocytes retrieved and fertilized and the live birth rate. Correlation between different parameters was calculated using Spearman's correlation coefficient. Receiver operating characteristic (ROC) curves were generated for AMH and AFC to compare ability of parameters to predict top quality or frozen embryos and the occurrence of a live birth. Results Of the 137 women who had fresh embryo transfer, 52 became pregnant (32.1% pregnancy rate per cycle started) and 38 had a live birth (23.5% live birth rate per cycle started). Both AMH and AFC had highly significant correlations with the number of oocytes retrieved and the number of oocytes fertilized ( P < 0.001). The two markers were also significantly associated with the number of top quality embryos available for transfer and the number of embryos frozen ( P < 0.01). With regard to live birth, AMH performed better than AFC ( P < 0.01 and P < 0.05, respectively), but both markers were more valuable in predicting the absence rather than the occurrence of live birth (negative predictive value 84%). Conclusions AMH and AFC are comparable predictors of oocytes retrieved and of the number of good quality embryos available for transfer and freezing. Prediction of live birth may help clinicians selecting patients suitable for single embryo transfer.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT)

Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized). In this randomised controlled trial (RCT), 220 patients with PCOS were randomly allocated in two groups: long GnRH agonist down-regulation protocol (n = 110) and flexible GnRH antagonist protocol (n = 110). No differences were observed in ongoing pregnancy rates [50.9 versus 47.3%, difference 3.6%, 95% confidence interval (CI): -9.6 to +16.8%] in the agonist and antagonist protocols, respectively. Incidence of OHSS Grade II was lower in the antagonist compared with agonist group (40.0 versus 60.0%, difference -20.0%, 95% CI: -7.1 to -32.9%, P < 0.01). Duration of stimulation (10 versus 12 days, difference 2 days, 95% CI: +1 to +2, P < 0.001) and total gonadotrophin required (1575 versus 1850 IU, difference -275 IU, 95% CI: -25 to -400, P < 0.05) were also lower in the antagonist compared with agonist protocol. The current RCT suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF. The study was registered at clinicaltrials.gov. ID: NCT00417144.

"hCG priming" effect in controlled ovarian stimulation through a long protocol

BackgroundRecently, it has been demonstrated that, in patients down-regulated by GnRH analogues (GnRHa), a short-term pre-treatment with recombinant LH (rLH), prior to recombinant FSH (rFSH) administration, increases the number of small antral follicle prior to FSH stimulation and the yield of normally fertilized embryos. However, no data exist in the literature regarding the potential beneficial effect of "hCG priming" in controlled ovarian hyperstimulation (COH) through a long GnRH-a protocol, which binds the same receptor (LH/hCGR), though it is a much more potent compared to LH. The primary aims of this study were to assess the effect of short-term pre-rFSH administration of hCG in women entering an ICSI treatment cycle on follicular development, quality of oocytes and early embryo development. The secondary endpoints were to record the effects on endometrial quality and pregnancy rate.MethodsPatients with a history of at least one previous unsuccessful ICSI cycle were randomly assigned into two groups to receive treatment with either a long protocol with rFSH (control group) or a long protocol with rFSH and pre-treatment with hCG (hCG group). In particular, in the latter group, a fixed 7 days course of 200 IU/day hCG was administered as soon as pituitary desensitization was confirmed.ResultsThe mean number of oocytes retrieved was not significantly different between the two treatment groups, although the percentage of mature oocytes tended to be higher but not significantly different in hCG-treated patients. The percentage of patients with more than one grade 3 embryos was higher in the pre-treatment group, which also showed a higher pregnancy rate.ConclusionAll the above clinical observations, in conjunction with previous data, suggest a point towards a beneficial "hCG priming" effect in controlled ovarian hyperstimulation through a long GnRH-a down-regulation protocol, particularly in patients with previous ART failures.

Vitrification is a highly efficient method to cryopreserve human embryos in in vitro fertilization patients at high risk of developing ovarian hyperstimulation syndrome

This study aimed to evaluate the efficacy of embryo vitrification as an emergency procedure for patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). A total of 69 embryos, derived from 24 patients for whom embryo transfer could not be performed because of the risk of developing OHSS, were vitrified and warmed for deferred embryo transfer. Surviving embryos were transferred, resulting in 10 clinical pregnancies, of which 4 were successfully delivered and the remaining 6 are still ongoing.

Results with early follicular phase recombinant luteinizing hormone supplementation during stimulation for in vitro fertilization

To study the effect of early follicular phase recombinant LH supplementation on stimulation outcome among women undergoing IVF using the GnRHa long protocol and recombinant FSH. Randomized, controlled trial. Private IVF unit. Women under the age of 40 with normal ovarian function undergoing their first or second IVF cycle. All stimulations followed the standard luteal long GnRHa down-regulation protocol. At suppression, patients in the experimental group received 75 IU of rLH daily for 4 days, and recombinant FSH at a fixed starting dose of 150 IU for the first 5 days was started a day later, on day 2 of rLH. In the control group, patients started rFSH at a fixed dose of 150 IU for the first 5 days at suppression. Baseline, stimulation, embryology parameters, and treatment outcome were compared. Of primary interest, recombinant FSH need during stimulation was assessed. Stimulation, embryology parameters, and treatment outcome were comparable. The amount of gonadotropins used and medication expense were similar in the two groups. Early follicular phase recombinant LH supplementation at a daily dose of 75 IU does not improve response to stimulation among normal responder women undergoing IVF.

Suboptimal response to GnRHa long protocol is associated with a common LH polymorphism

The aim of this observational preliminary trial was to estimate the association between the most common polymorphism of LH (LH-β variant: v-βLH), with different profiles of ovarian response to recombinant human FSH (rhFSH). A total of 60 normogonadotrophic patients undergoing a gonadotrophin-releasing hormone analogue long down-regulation protocol followed by stimulation with recombinant human FSH (rhFSH) for IVF/intracytoplasmic sperm injection, and in whom at least five oocytes were retrieved were retrospectively included. On the basis of the total rhFSH consumption, patients were divided into three groups: Group A: 22 women requiring a cumulative dose of rhFSH >3500 IU; Group B: 15 patients requiring 2000–3500 IU; Group C (control): 23 women requiring <2000 IU. The presence of v-βLH was evaluated using specific immunoassays. Peak oestradiol concentrations were significantly lower in Group A when compared with both groups B ( P< 0.05) and C ( P< 0.001). Group A had a significantly lower ( P< 0.05) number of oocytes retrieved (7.3 ± 1.5, 11.7 ± 2.4 and 14.7 ± 4.1 in the three groups, respectively). Seven carriers (31.8%) of v-βLH were found in Group A, whereas only one variant (6.7%) was observed in Group B; no variant was detected in Group C. These preliminary results suggest that v-βLH is more frequent in women with ovarian resistance to rhFSH.

A proteomic analysis of IVF follicular fluid in women ≤32 years old

To address the lack of predictors of IVF success by using proteomic biometrics. Experimental study of follicular fluid specimens from a prospective cohort of IVF patients. Academic research laboratory and IVF program. Women <or=32 years old with <11 oocytes retrieved and no pregnancy were matched to women who had >or=11 oocytes and live birth (10 pairs). Year of cycle start and IVF down-regulation protocol were also matched. Follicular fluid was separated by two-dimensional polyacrylamide gel electrophoresis followed by Sypro Ruby staining and comparison with PDQuest software. Logistic regression was incorporated to calculate the likelihood of live birth in relation to the protein spot of interest. Protein markers. Liquid chromatography-tandem mass spectrometry and searching of sequence databases revealed 11 potential protein candidates. Haptoglobin alpha, predominantly fetal expressed T1 domain, mitochondrial integrity genome (ATPase), apolipoprotein H (beta-2 glycoprotein I), dihydrolipoyl dehydrogenase, lyzozyme C, fibrinogen alpha-chain, and immunoglobulin heavy chain V-III (region BRO) were found to have increased expression in the live birth group, whereas antithrombin, vitamin D-binding protein, and complement 3 were decreased. An ELISA confirmed a significantly lower level of antithrombin. Proteomic evaluation of follicular fluid is able to identify potential biomarkers of good versus poor responders in matched pairs of IVF patients.

Follitropin-α (Gonal-F) versus follitropin-β (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?

In an attempt to examine and compare the effect of the two commercially available recombinant FSH on ovarian stimulation characteristics and IVF cycle outcome, we studied 264 IVF cycles in patients with a favorable prognosis a priori, 198 in patients using follitropin-alpha, and 68 in patients using follitropin-beta. Although both groups achieved a comparable number of retrieved oocytes, the use of follitropin-beta was associated with a tendency toward a lower clinical pregnancy rate (PR), and with significantly higher E(2) levels despite the use of significantly lower total gonadotropin dose.

Increasing mid-follicular hCG levels in IVF/ICSI patients stimulated with HP-hMG leads to higher live birth rates

OBJECTIVE: A recent meta-analysis has reported that menotropins are associated with a significant 4% increase in live birth rate compared to recombinant FSH in IVF/ICSI treatment following a long downregulation protocol (Coomarasamy et al, Hum Reprod 2008, 23: 310-5). This difference may be attributed to the presence of LH-activity in menotropins. hCG is the main component of the LH-activity in the highly purified menotropin (HP-hMG) preparation MENOPUR. Data from a single large trial have shown that hCG concentrations on day 6 of stimulation with this HP-hMG preparation were an independent positive predictor of live birth in IVF cycles (Arce et al, Hum Reprod 2006; 21(S1): i141-2). The objective of this investigation was to evaluate if additional clinical trial data support this finding. DESIGN: Retrospective analysis of two randomized controlled trials that have analysed hCG levels on day 6 of stimulation and followed patients until delivery. MATERIALS AND METHODS: This analysis included 736 women undergoing stimulation with HP-hMG in an IVF/ICSI cycle (n=491 for IVF, n=245 for ICSI) in two trials [EISG, Fertil Steril 2002, 78: 520-8; Nyboe Andersen et al, Hum Reprod 2006, 21: 3217-27]. hCG was analysed by a central laboratory (LKF, Raisdorf, Germany) using an electrochemiluminescence immunoassay. Patients were grouped in quartiles (<25%, 25-50%, 50-75%, >75%) within each study according to the hCG level on day 6 of stimulation. RESULTS: Demographics and baseline characteristics were comparable across hCG quartiles, with the exception of higher day 6 hCG concentrations in patients with lower weight and body mass index.The live birth rate for patients undergoing controlled ovarian hyperstimulation with HP-hMG increased significantly with increasing day 6 hCG level with an odds ratio of 1.45 (95% confidence interval: 1.19-1.77; p<0.001). Overall, the live birth rate for IVF/ICSI patients with a day 6 hCG level in the lowest quartile was 12%. This increased to a live birth rate of 25% for patients with the mid-follicular hCG level in the 25-50% quartile, 27% in the 50-75% quartile, and 31% for the patients in the highest day 6 hCG quartile. There was no heterogeneity between the two studies. CONCLUSIONS: Increasing concentrations of hCG on day 6 of stimulation are associated with a significantly higher live birth rate in IVF/ICSI cycles following a long downregulation protocol and ovarian stimulation with HP-hMG.

The effects of different protocols of controlled varian hyperstimulation on pregnancy outcomes in the patients with diminished ovarian reserve

OBJECTIVE: Several approaches have been described for the patients who diminished with ovarian reserve. At the present, the standard long protocol and short down-regulation (flare up) protocol are mainly used. The objective of the present study was to compare the effects of different protocols in controlled ovarian hyperstimulation using GnRH-a/HMG/rFSH long protocol, short protocols and GnRH-antagonist protocol for the patients who with diminished ovarian reserve.DESIGN: Prospective randomized study.MATERIALS AND METHODS: One hundred and twenty-three patients who diagnosed with diminished ovarian reserve were enrolled in this study. All patients underwent 123 fresh in vitro fertilization (IVF) and embryo transfer (ET) cycles. The mean age was 34.4±4.5 years-old. All the patients were divided randomly into 3 groups. Group 1: Standard long protocol (GnRH-a/HMG/rFSH) (40 completed cycles); Group 2: Flare up protocol (GnRH-a/HMG/rFSH) (53 completed cycles); Group 3: GnRH-antagonist protocol (30 completed cycles). The number of oocytes retrieved, clinical pregnancy and implantation rates were compared among 3 groups.RESULTS: The number of oocytes retrieved was not different among 3 groups (9.2±4.4, 9.0±7.0, and 10.4±8.0, respectively). The clinical pregnancy rates were 20.0%, 30.2% and 30.0% in 3 groups, respectively, and in Group 1 was significantly lower (P<0.05) than other 2 groups. The implantation rate was significantly lower in Group 1 compared with other 2 Groups (10.3%, 16.4% and 21.2% respectively, P<0.05).CONCLUSIONS: The present study indicates that GnRH-a short protocol is suitable for the patients with diminished ovarian reserve. GnRH-antagonist protocol is also an alternative method in the patients with diminished ovarian reserve. OBJECTIVE: Several approaches have been described for the patients who diminished with ovarian reserve. At the present, the standard long protocol and short down-regulation (flare up) protocol are mainly used. The objective of the present study was to compare the effects of different protocols in controlled ovarian hyperstimulation using GnRH-a/HMG/rFSH long protocol, short protocols and GnRH-antagonist protocol for the patients who with diminished ovarian reserve. DESIGN: Prospective randomized study. MATERIALS AND METHODS: One hundred and twenty-three patients who diagnosed with diminished ovarian reserve were enrolled in this study. All patients underwent 123 fresh in vitro fertilization (IVF) and embryo transfer (ET) cycles. The mean age was 34.4±4.5 years-old. All the patients were divided randomly into 3 groups. Group 1: Standard long protocol (GnRH-a/HMG/rFSH) (40 completed cycles); Group 2: Flare up protocol (GnRH-a/HMG/rFSH) (53 completed cycles); Group 3: GnRH-antagonist protocol (30 completed cycles). The number of oocytes retrieved, clinical pregnancy and implantation rates were compared among 3 groups. RESULTS: The number of oocytes retrieved was not different among 3 groups (9.2±4.4, 9.0±7.0, and 10.4±8.0, respectively). The clinical pregnancy rates were 20.0%, 30.2% and 30.0% in 3 groups, respectively, and in Group 1 was significantly lower (P<0.05) than other 2 groups. The implantation rate was significantly lower in Group 1 compared with other 2 Groups (10.3%, 16.4% and 21.2% respectively, P<0.05). CONCLUSIONS: The present study indicates that GnRH-a short protocol is suitable for the patients with diminished ovarian reserve. GnRH-antagonist protocol is also an alternative method in the patients with diminished ovarian reserve.

Luteal phase bleeding (LPB) in in vitro fertilization (IVF) cycles supplemented with crinone 8% intravaginal gel (CR) or intramuscular progesterone (IMP)

OBJECTIVE: To identify incidence of LPB in IVF cycles supplemented with either CR or IMP and to correlate it with pregnancy outcomes.DESIGN: Planned Interim Analysis of a prospective randomized controlled study.MATERIALS AND METHODS: Women under age 40 with day 3 FSH values <15 mIU/ml undergoing their first, second or third IVF cycle with GnRH agonist downregulation protocol were stratified by age (<35 and 35-39) and randomized to receive either CR or IMP 48 or 24 hours after oocyte retrieval respectively. Patients were phone surveyed at cycle completion regarding incidence of LPB. Pregnancy rates per embryo transfer, miscarriage rates (SAB) and incidence of LPB relative to pregnancy outcome were recorded and analyzed. Two-sided Wald p-values, adjusted for age, were calculated using logistic regression.Table 1Pregnancies, SABs and BleedingOUTCOMELPB N=70 (%)NO LPB N=116 (%)PPregnant (N=119)31/70 (44)88/116 (76)<0.0001SAB (N=31)12/31 (39)19/88 (22)0.07 Open table in a new tab Table 2LPB and Pregnancy Outcomes with CR and IMPOUTCOMECR N=94 (%)IMP N=92 (%)PLPB41/94 (44)29/92 (32)0.08Pregnant61/94 (65)58/92 (63)0.78Pregnant among LPB18/41 (44)13/29 (45)0.96Pregnant among Non-LPB43/53 (81)45/63 (71)0.23SAB17/61 (28)14/58 (24)0.65SAB among LPB9/18 (50)3/13 (23)0.13SAB among Non-LPB8/43 (19)11/45 (24)0.50LPB among Pregnant18/61 (30)13/58 (22)0.38LPB among Non-Pregnant23/33 (70)16/34 (47)0.06LPB among SAB9/17 (53)3/14 (21)0.07LPB among Ongoing Pregnancy9/44 (20)10/44 (23)0.80 Open table in a new tab CONCLUSIONS: 1. LPB is a poor prognostic sign for ongoing pregnancy in IVF; the ongoing pregnancy rate among patients with LPB is not different between CR and IMP. 2. Pregnancy and SAB rates were similar between CR and IMP. 3. The increased LPB with CR observed in this trial occurred in unsuccessful cycles (non-pregnant and SAB). 4. IMP delays bleeding in unsuccessful cycles (non-pregnant and SAB). OBJECTIVE: To identify incidence of LPB in IVF cycles supplemented with either CR or IMP and to correlate it with pregnancy outcomes. DESIGN: Planned Interim Analysis of a prospective randomized controlled study. MATERIALS AND METHODS: Women under age 40 with day 3 FSH values <15 mIU/ml undergoing their first, second or third IVF cycle with GnRH agonist downregulation protocol were stratified by age (<35 and 35-39) and randomized to receive either CR or IMP 48 or 24 hours after oocyte retrieval respectively. Patients were phone surveyed at cycle completion regarding incidence of LPB. Pregnancy rates per embryo transfer, miscarriage rates (SAB) and incidence of LPB relative to pregnancy outcome were recorded and analyzed. Two-sided Wald p-values, adjusted for age, were calculated using logistic regression. CONCLUSIONS: 1. LPB is a poor prognostic sign for ongoing pregnancy in IVF; the ongoing pregnancy rate among patients with LPB is not different between CR and IMP. 2. Pregnancy and SAB rates were similar between CR and IMP. 3. The increased LPB with CR observed in this trial occurred in unsuccessful cycles (non-pregnant and SAB). 4. IMP delays bleeding in unsuccessful cycles (non-pregnant and SAB).

Autoimmune response to Chlamydia trachomatis infection and in vitro fertilization outcome

This observational study was conducted in 235 patients undergoing IVF who had a cervical swab positive for Chlamydia trachomatis and who underwent antibiotic treatment until a negative cervical swab before IVF attempt. After oocyte retrieval, follicular fluids of 109 patients out of 228 still showed the presence of IgA antichlamydia antibodies and a significantly lower pregnancy and implantation rate; therefore we conclude that patients should undergo IVF procedure after serum antichlamydia IgA tests negative.

Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles

The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles. An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using the likelihood ratio test in a logistic regression analysis. The live birth rate per cycle initiated was 26.5% (130/491) with HP-HMG and 20.8% (103/495) with rFSH ( P = 0.041). The odds ratio in favour of HP-HMG was 1.36 (95% confidence interval: 1.01–1.83). Thus, the findings of this integrated analysis demonstrate that ovarian stimulation with HP-HMG, following a long down-regulation protocol, in IVF cycles results in significantly more live births than stimulation with rFSH alone.

Urinary hMG versus recombinant FSH for controlled ovarian hyperstimulation following an agonist long down-regulation protocol in IVF or ICSI treatment: a systematic review and meta-analysis

Since the most recent Cochrane review on hMG versus rFSH for controlled ovarian hyperstimulation following a long down-regulation protocol, several new trials have emerged. We conducted a systematic review and meta-analysis of randomized trials comparing the effectiveness of hMG versus rFSH following a long down-regulation protocol in IVF-ICSI cycles, on the primary outcome of live birth per woman randomized, as well as several other secondary outcomes. Searches were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts (last search January 2007). Seven randomized trials, consisting of a total of 2159 randomized women, were identified. A meta-analysis of these trials showed a significant increase in live birth rate with hMG when compared with rFSH (relative risk, RR = 1.18, 95% CI: 1.02-1.38, P = 0.03). The heterogeneity test was non-significant (P = 0.97), suggesting that there was no statistical inconsistency between the seven studies. The pooled risk difference (RD) for the outcome of live birth rate was 4% (95% CI: 1-7%) for these study populations. There was an increase in clinical pregnancy rates with hMG when compared with rFSH (RR = 1.17, 95% CI 1.03-1.34). No significant differences were noted for gonadotrophin use, spontaneous abortion, multiple pregnancy, cancellation and ovarian hyperstimulation syndrome rates. For the populations in the randomized trials, hMG was associated with a pooled 4% increase in live birth rate when compared with rFSH in IVF-ICSI treatment following a long down-regulation protocol.