Recombinant human FSH versus highly purified urinary FSH: a randomized study in intrauterine insemination with husbands' spermatozoa

A randomized trial was carried out comparing recombinant FSH (rFSH) and highly purified urinary FSH (uFSH) in intrauterine insemination (IUI) with husbands' spermatozoa. A total of 45 women received rFSH (139 cycles), while 46 women received uFSH (155 cycles). The starting dose was 150 IU/day s.c., beginning on the second day, and on days 6-7 the dose was adjusted according to ovarian response, assessed by vaginal ultrasound and plasma oestradiol concentration. The pregnancy rate according to the intention to treat was 57.8% in rFSH versus 52.2% in uFSH, the corrected pregnancy rates 56.8% and 52.2%, and the cumulative pregnancy rates 69.6% and 61.0%, but the differences were not statistically significant. The per cycle pregnancy rate was 18.12% in rFSH and 15.48% in u-FSH, also not statistically significant. In the rFSH group, the consumption of FSH ampoules per cycle was significantly lower (19.20 +/- 7.02 versus 23. 80 +/- 10.78; P < 0.0001). The ratio of oestradiol/FSH ampoules was significantly higher in rFSH (56.45 +/- 31.26 versus 46.41 +/- 29. 25; P < 0.001). These data indicate that, in IUI cycles, rFSH has a higher potency than uFSH.     

Comparison of different gonadotrophin preparations in intrauterine insemination cycles for the treatment of unexplained infertility: a prospective, randomized study

BACKGROUND: A comparison of the effectiveness of different gonadotrophin preparations in intrauterine insemination (IUI) cycles for patients with unexplained infertility was performed. METHODS: Two hundred and forty-one patients were prospectively randomized using computer-generated random numbers into three groups: 81 in the Follitropin alpha (Group I), 80 in the urinary FSH (uFSH) (Group II) and 80 in the hMG (Group III). The primary outcome was clinical pregnancy rate with duration of stimulation, total gonadotrophin dose, number of dominant follicles, clinical pregnancy rate, multiple pregnancy, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate being secondary outcomes. RESULTS: Clinical pregnancy rate was significantly higher in the rFSH group (25.9% in Follitropin alpha, 13.8% in uFSH and 12.5% in HMG groups; P = 0.04). There was no significant difference in terms of duration of stimulation, but mean FSH dose consumed per cycle was significantly lower in the recombinant FSH (rFSH) group compared with others (825 IU in Follitropin alpha, 1107 IU in uFSH and 1197 IU in HMG groups; P = 0.001). The number of follicles > or =16 mm diameter was significantly higher in the rFSH group compared with the uFSH and HMG groups (2.6 in Follitropin alpha, 1.3 in uFSH and 1.4 in HMG groups; P = 0.001). CONCLUSION: rFSH may result in a better outcome in IUI cycles for unexplained infertility.     

Recombinant FSH in alternative doses or versus urinary gonadotrophins for ovulation induction in subfertility associated with polycystic ovary syndrome: a systematic review based on a Cochrane review

This paper is based on a Cochrane review published in The Cochrane Library, issue 2, 2001 (see www.CochraneLibrary. net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. This systematic review was performed to study the efficacy and safety of recombinant FSH (rFSH) versus urinary FSH (uFSH) and to compare different dose regimens of rFSH for ovulation induction in women with clomiphene-resistant polycystic ovary syndrome (PCOS). Six randomized controlled trials were included in the review, according to the principles of the Cochrane Menstrual Disorders and Subfertility Group. Three trials compared rFSH with uFSH and three trials compared two different treatment regimens of rFSH. Participants were women with clomiphene citrate-resistant PCOS. Main outcome measures were ovulation, clinical pregnancy, miscarriage, multiple pregnancy, ovarian stimulation syndrome (OSS), total gonadotrophin dose used and total duration of stimulation. Summary statistics were expressed as odds ratios. Data from the trials comparing rFSH and uFSH could be pooled. There was no evidence of a difference between rFSH and uFSH in any of the outcomes. Data from the trials comparing different dose regimens of rFSH could not be combined, and for each comparison there was insufficient evidence of a difference. More randomized clinical trials with sufficient power are necessary to estimate the difference, if one exists, between rFSH and uFSH and between different dose regimens of rFSH.     

The use of metformin for women with PCOS undergoing IVF treatment

BACKGROUND: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF. METHODS: A randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate. RESULTS: One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022). CONCLUSION: Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.     

Meta-analysis of recombinant versus urinary-derived FSH: an update

BACKGROUND: The study aim was to analyse the results of randomized controlled trials (RCTs) comparing recombinant FSH and urinary-derived FSH gonadotrophins [hMG, urinary purified FSH (FSH-P) and highly purified FSH (FSH-HP)] in an IVF/ICSI programme. METHODS: All published truly RCTs using a long protocol of GnRH agonists for down-regulation, were reviewed. Data of pregnancy rate per started cycle were extracted, and odds ratios (OR) calculated using a fixed effect model. Subgroup analysis was carried out to compare recombinant FSH (rFSH) with each product (hMG alone, FSH-P alone and FSH-HP alone). RESULTS: There was no statistically significant difference in the pregnancy rate per started cycle between rFSH and urinary-derived FSH gonadotrophins (OR 1.07; 95% CI 0.94-1.22). Subgroup analysis showed no statistically significant difference in the pregnancy rate per started cycle between rFSH versus hMG (OR 0.81; 95% CI 0.63-1.05), rFSH versus FSH-P (OR 1.24; 95% CI 0.98-1.58) and rFSH versus FSH-HP (OR 1.14; 95% CI 0.94-1.40). There was no significant heterogeneity of treatment effect across the trials. CONCLUSIONS: There is no evidence of clinical superiority in clinical pregnancy rate for rFSH over different urinary-derived FSH gonadotrophins. Additional factors should be considered when choosing a gonadotrophin regimen, including the cost, patient acceptability, safety and drug availability.     

A comparison of ICSI outcomes with fresh and cryopreserved epididymal spermatozoa from the same couples

The published experience with frozen-thawed epididymal spermatozoa and intracytoplasmic sperm injection (ICSI) suggests that fertilization and pregnancy success rates are comparable to those achieved with freshly retrieved spermatozoa. However, no study has exactly compared clinical outcomes between the two IVF/ICSI cycles in the same couples. To formally address this issue, we assessed ICSI outcomes in couples each of whom had had two IVF/ICSI cycles: one using fresh and the second using frozen-thawed epididymal spermatozoa obtained from a single aspiration procedure. From a pool of 101 consecutive patients undergoing IVF/ICSI with epididymal spermatozoa, 19 couples initially used fresh epididymal spermatozoa and subsequently underwent a second IVF/ICSI procedure with frozen-thawed spermatozoa from the same aspiration. Normal (2PN) oocyte fertilization rates, embryo quality and pregnancy rates were compared between the two IVF/ICSI cycles for each couple. In the fresh epididymal sperm group, 58.4% of the injected oocytes fertilized normally compared with 62.0% of the injected oocytes in the frozen-thawed epididymal sperm group, revealing no statistically significant difference. Graded embryo quality also did not differ significantly between the paired IVF/ICSI cycles. The clinical pregnancy rates were 31.6% (6/19) and 36.8% (7/19) in the first and second cycles respectively. All but one pregnancy were singletons. In summary, this study provides strong evidence to support the notion that motile, cryopreserved and thawed epididymal spermatozoa are equal to freshly retrieved spermatozoa for ICSI in couples with obstructive azoospermia.     

Cost-effectiveness modelling of recombinant FSH versus urinary FSH in assisted reproduction techniques in the UK.

BACKGROUND: The purpose of this study was to undertake an economic evaluation to compare the cost-effectiveness of recombinant (r)FSH with urinary (u)FSH for attaining clinical pregnancy with assisted reproduction. METHODS: Mathematical modelling was utilized incorporating a Markovian decision framework and a Monte Carlo simulation. Statistical representations of recurrent events over time were incorporated into a decision analysis involving fresh and frozen cycles in any sequence (after the first fresh embryo transfer cycle) over three successive assisted reproduction attempts. The mean values of transition probabilities were derived from randomized controlled clinical trials and published reports. The distributions of these transition probabilities were agreed upon by a panel of experts. Cost data for procedures and drugs were derived and validated according to the perspectives of the National Health Service and private clinics in the UK. RESULTS: The study involved 5000 Monte-Carlo simulations of treatment on a Markov cohort of 100 000 patients. The total number of pregnancies attained was significantly higher in the rFSH (40 575) compared with the uFSH (37 358) group. The cost per successful pregnancy was significantly lower for rFSH (5906 pounds sterling) compared with uFSH (6060 pounds sterling) and overall, fewer cycles of treatment were required with rFSH to achieve an ongoing pregnancy. The incremental cost-effectiveness ratio is 4148 pounds sterling for each additional clinical pregnancy with rFSH. CONCLUSIONS: In addition to the increased effectiveness of rFSH in ART, this study demonstrated that it is more cost-effective and more efficient than uFSH in attaining an ongoing pregnancy.     

Human cumulus-free oocyte maturational profile and in vitro developmental potential after stimulation with recombinant versus urinary FSH

BACKGROUND: This study compares the influence of recombinant (r)FSH and urinary (u)FSH stimulation on oocyte and embryo quality in patients undergoing ICSI. METHODS AND RESULTS: Denuded oocyte maturity in ICSI patients was graded on a scale from metaphase II (MII) to prophase for nuclear maturation of oocytes. The relationships of cumulus-free oocyte maturational profiles with in vitro outcome parameters were evaluated. In the study population with an unknown distribution of FSH receptor polymorphisms, the ovarian response to rFSH stimulation was significantly different from that of uFSH stimulation, including lower number of oocytes retrieved/oocytes in MII, higher fertilization rates and higher good quality embryo rates. In the study population with a similar distribution of FSH receptor polymorphisms, the ovarian responses to rFSH were lower numbers of oocytes in MII, higher fertilization rates and higher good quality embryo rates, but the total number of oocytes retrieved was not influenced, in comparison with ovarian stimulation with uFSH. CONCLUSIONS: rFSH stimulation appears to influence oocyte quality and subsequent embryo quality in comparison with uFSH stimulation. FSH receptor polymorphisms seem to be an intrinsic factor influencing the ovarian response to FSH stimulation.     

Rescue ICSI of oocytes that failed to extrude the second polar body 6 h post-insemination in conventional IVF

BACKGROUND: Attempts to 'rescue' by ICSI oocytes that remained unfertilized 24 h after conventional IVF have generally resulted in poor outcomes. The aim of the present study was to compare the outcome of rescue ICSI performed on one group of patients 6 h after initial insemination with those of another group where rescue ICSI was performed 22 h after initial insemination. METHODS: Twenty-five patient IVF cycles provided the oocytes for rescue ICSI 6 h after initial insemination, and 20 cycles provided the oocytes for rescue ICSI 22 h after initial insemination in this retrospective study. Fertilization and cleavage rates, embryo quality, implantation, and pregnancy rates after rescue ICSI were the main outcome measures. RESULTS: A fertilization rate of 70.3% was achieved with 6 h rescue ICSI compared with 48.5% with 22 h rescue ICSI (P < 0.0001). From 6 h rescue ICSI, 12 clinical pregnancies (48.0%) resulted in three sets of twins, eight singletons and one abortion. From 22 h rescue ICSI there was one (5.0%) singleton pregnancy and delivery of a healthy baby. Likewise, the implantation rate was 20.2% from 6 h rescue ICSI compared with 1.72% from 22 h rescue ICSI (P < 0.02). CONCLUSIONS: Rescue ICSI after 6 h post-insemination (46 h post-HCG) gave better fertilization, pregnancy and implantation rates compared with rescue ICSI after 22 h when oocytes have become aged.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.     

Assisted reproductive technology in Europe, 2000. Results generated from European registers by ESHRE

European results of assisted reproductive techniques from treatments initiated during 2000 are presented in this fourth annual report. Data were collected mainly from pre-existing national registers. From 22 countries, 569 clinics reported 279 267 cycles: IVF 126 961, ICSI 99 976, frozen embryo replacement (FER) 45 800 and oocyte donations (OD) 6530. In nine countries where all clinics reported to the register, a total of 142 174 cycles were performed in a population of 166 million, corresponding to 856 cycles per million inhabitants. After IVF and ICSI, the distribution of transfer of one, two, three and >or=4 embryos was 12.1, 46.7, 33.3 and 6.8%, respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per aspiration and per transfer was 24.7 and 28.4%, respectively. For ICSI, the corresponding rates were 26,6% and 28,7%. These figures represent increases of 0.7 and 0.8% compared with 1999. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.6, 24.4, 2.0 and 0.04%. This gives a total multiple delivery rate of 26.4%. The range of triplet deliveries after IVF and ICSI ranged from 0.3 to 7.0% between countries. Compared with 1999, the number of reported cycles was increased by 8% and the clinical pregnancy rate per transfer was increased by 0.7% after IVF and by 0.8% after ICSI. The total multiple delivery rates after IVF and ICSI remain unchanged during the last 4 years.     

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). METHODS: A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. RESULTS: The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. CONCLUSION: rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.     

Outcome of conventional IVF and ICSI on sibling oocytes in mild male factor infertility

BACKGROUND: Decisions concerning the treatment choice for assisted reproduction (IVF or ICSI) are usually made after the evaluation of male fertility factors, or after taking into account the results of previous IVF attempts. There are no widely accepted criteria, so decisions for couples with male subfertility are often empirical and may lead to complete fertilization failure after IVF, or to the unnecessary use of ICSI. METHODS: A study was conducted in which half the oocytes from each of 58 couples with moderate oligo +/- astheno +/- teratozoospermia were inseminated (conventional IVF) and the other half microinjected (ICSI). The technique used for subsequent cycles depended on the results of the first cycle. RESULTS: Nineteen of the 58 IVF/ICSI attempts resulted in fertilization after ICSI only (32.8%) and 39 in fertilization after IVF and ICSI (67.2%). For patients with oocyte fertilization only after ICSI, 61.5% of the oocytes microinjected were fertilized. A mean of 2.2 embryos per patient were transferred, leading to eight clinical pregnancies (42.1%).The implantation rate was 21.4%. All subsequent cycles were carried out with ICSI. Couples with oocyte fertilization after both IVF and ICSI had slightly better semen characteristics than those with oocyte fertilization only after ICSI, but this difference was not significant. Overall, no statistically significant difference was observed between IVF and ICSI in sibling oocytes for any of the variables studied: fertilization rate, embryo morphology and rates of development, pregnancy and implantation. Although only small numbers of oocytes or embryos were available for each couple, six couples had lower fertilization rates after IVF and eight had lower embryo quality after IVF. Eight patients had lower sperm quality in the second cycle, and only seven couples underwent subsequent IVF cycles. CONCLUSIONS: This strategy enabled us to avoid 32.8% of complete fertilization failures after IVF, but not to decrease significantly the number of ICSI attempts in subsequent cycles. However, the uncertainties concerning the safety of ICSI suggest that ICSI should be used cautiously and judiciously.     

Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE

European results of assisted reproductive techniques from treatments initiated during 1999, are presented in this third report. Data were collected mainly from pre-existing national registers. From 22 countries 538 clinics reported 258 460 cycles: IVF 125 370, ICSI 95 221, frozen embryo replacement (FER) 34 002 and oocyte donations (OD) 3867. In eight countries, where all clinics reported to the register, a total of 99 629 cycles was performed in a population of nearly 106 million, corresponding to 943 cycles per million inhabitants and 3.9 cycles per 1000 women aged 15-49 years. After IVF and ICSI the distribution of transfer of 1, 2, 3 and >or=4 or more embryos was 11.9, 39.2, 39.6 and 9.3% respectively. Huge differences existed between countries. For IVF the clinical pregnancy rate per aspiration and per transfer was 24.2 and 27.7% respectively. For ICSI the corresponding rates were 26.1 and 27.9%. These figures represent relative increases by 2.2 to 5.2% compared with 1998. The distribution of singleton, twin, triplet and quadruplet deliveries for IVF and ICSI combined was 73.7, 24.0, 2.2 and 0.1%. This gives a total multiple delivery rate of 26.3%. Triplet deliveries after IVF and ICSI ranged from 0.3-7.0% between countries. Compared with 1998, the number of reported cycles increased by 11% and the clinical pregnancy rate per transfer increased from 27.0 to 27.7% after IVF and from 26.8 to 27.9% after ICSI. Multiple deliveries after IVF and ICSI remained unchanged at 26.3% in 1999.     

Induction of ovulation in women undergoing assisted reproductive techniques: recombinant human FSH (follitropin alpha) versus highly purified urinary FSH (urofollitropin HP)

This multicentre, open, randomized, study compared the efficacy and safety of recombinant follicle stimulating hormone (rFSH; follitropin alpha) with highly purified urinary human FSH (uFSH; urofollitropin HP) in women undergoing ovulation induction for assisted reproductive techniques. Following long down-regulation with buserelin, patients received two ampoules of 75 IU (150 IU) s.c. rFSH or highly purified uFSH for 6 days, after which the dose could be increased until they fulfilled the criteria for human chorionic gonadotrophin (HCG) administration. Of 168 patients recruited, 155 received at least one dose of FSH, and 137 received HCG [68: rFSH (85%); 69: uFSH (92%)]. Following oocyte retrieval and fertilization, up to three embryos were replaced/patient and luteal support was given. The mean number of oocytes retrieved/patient was 10.2 +/- 6.0 for rFSH patients compared with 10.8 +/- 6.1 in the uFSH group (not significant). There was a trend towards fewer ampoules used (22.3 +/- 6.5 versus 24.3 +/- 6.5), higher pregnancy (44.3 versus 41.4%) and live birth rates (33.8 versus 26.7%), as well as a lower miscarriage rate (0.0 versus 16.7%) in favour of rFSH. However, no significant differences in efficacy parameters were recorded. Ovarian hyperstimulation syndrome occurred in 8.6% and 7.9% of rFSH and uFSH patients respectively. In conclusion, this protocol was effective in inducing multiple follicular development and high numbers of oocytes were retrieved with both drugs.     

Andrology: Micromanipulation improves in-vitro fertilization results after epididymal or testicular sperm aspiration in patients with congenital absence of the vas deferens

In all, 58 couples suffering from infertility because of congenitalbilateral absence of the vas deferens underwent a total of 67combined microsurgical epididymal aspiration or testicular spermextraction (TESE) and in-vitro fertilization (TVT) treatments.The oocytes recovered were inseminated by either the microdropletIVF technique (n=20), subzonal insemination (SUZI; n= 10) orintracyto-plasmic sperm injection (ICSI; n= 37). Of the ICSIcycles, 12 were performed using spermatozoa obtained by TESE.Fertilization rates for epididymal spermatozoa were significantlyhigher for SUZI (17.9%, 17/95) and ICSI (34.4%, 137/398) thanfor microdroplet IVF (5.2%, 18/343) cycles. The proportion ofcycles in which fertilization was achieved was higher in theSUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%).Delivery or an ongoing pregnancy was achieved in one (5%) IVFcycle, two (20%) SUZI cycles and seven (18.9%) ICSI cycles.SUZI or ICSI using epididymal or testicular spermatozoa significantlyimproved the oocyte fertility rate. The ICSI procedure was especiallyadvantageous in patients for whom spermatozoa were obtainedfrom a testicular biopsy.     

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

A comparison of four different techniques of assisted hatching

BACKGROUND: Assisted hatching (AH) has been proposed as a means to increase the implantation rate in patients with poor prognosis for pregnancy. The procedure appears to be effective when used selectively. Several different methods for AH have been introduced over the years but comparative studies are lacking. The aim of the current study was to compare retrospectively the efficacy of AH performed with four different methods in patients undergoing IVF or ICSI. METHODS: AH was performed prior to day 3 embryo transfer in 794 IVF/ICSI cycles. Indications for AH were females aged >35 years and/or elevated follicular phase FSH levels, previous failed IVF/ICSI cycles, poor embryo quality, and thick zona pellucida (>15 microm). Assignment to one of the four methods of AH was according to the availability of the particular method during the study period. The study was not randomized. RESULTS: Partial zona dissection was used in 239, acid Tyrode in 191, diode laser in 219 and pronase thinning of the zona pellucida in 145. Mean female age, mean number of previous failed IVF/ICSI cycles, number of oocytes retrieved, fertilization and cleavage rates, good quality embryos and zona thickness on day 3 did not differ between groups. Mean number of embryos transferred, implantation rate, clinical pregnancy rate, and abortion rates were likewise similar. CONCLUSIONS: Selective AH using four different methods yields similar implantation and pregnancy rates.     

Recombinant follicle stimulating hormone stimulation in poor responders with normal basal concentrations of follicle stimulating hormone and oestradiol: improved reproductive outcome.

A total of 30 young infertile patients who exhibited a poor response in two previous consecutive cycles, despite having normal basal follicle stimulating hormone (FSH) and oestradiol concentrations, were invited to participate in a prospective randomized study comparing the clinical efficacy of recombinant (rFSH) and urinary (uFSH) follicle stimulating hormone. An evaluation of the total dose used (3800 IU versus 4600 IU, P < 0.05) and duration of treatment (10.2 days versus 13.2 days, P < 0.05) showed a significantly shorter treatment period as well as a significantly lower total dose of FSH required to induce ovulation successfully in the group of patients treated with rFSH. Significantly more oocytes (7.2 versus 5. 6, P < 0.05) as well as mature oocytes (5.9 versus 3.2, P < 0.01) were retrieved after rFSH treatment. In addition, significantly more good quality embryos were obtained (3.4 versus 1.8, P < 0.05) in the group of patients treated with rFSH and, as a result, higher pregnancy (33 versus 7%, P < 0.01) and implantation (16 versus 3%, P < 0.01) rates were achieved in these patients. It is concluded that rFSH is more effective than uFSH in inducing multifollicular development and achieving pregnancy in young low responders.     

Day 2 elective single embryo transfer in clinical practice: better outcome in ICSI cycles

BACKGROUND: Single embryo transfer (SET) after IVF/ICSI has been shown to result in an acceptable pregnancy rate in selected subjects. In our unit, SET is routinely carried out among women under the age of 36 in the first or second treatment cycle when a top-quality embryo is available. In order to define further the selection criteria for SET, we have analysed the outcome of elective SET (eSET), including the cumulative pregnancy rate after frozen embryo transfers, performed in the years 2000-2002 in the Oulu Fertility Center. METHODS: During the study period, a total of 1271 transfers were performed, and in 468 cycles SET (39% of all transfers) was carried out. Of the SET cycles, in 308 cases a top-quality embryo was transferred on day 2 and extra embryos were frozen. Of these eSET cycles, ICSI was carried out in 87 cycles (28%). RESULTS: The overall clinical pregnancy rate per transfer was 34.7% in the eSET cycles. In the eSET ICSI cycles, the clinical pregnancy rate was significantly higher than in the corresponding IVF cycles (50.6 versus 28.5%, P < 0.001). The cumulative pregnancy rate per patient after fresh and frozen embryo transfers was also significantly higher after ICSI (71.2 versus 53.4%, P < 0.01). CONCLUSIONS: A high cumulative pregnancy rate per oocyte retrieval can be achieved after eSET in daily clinical practice. The implantation rate of fresh top-quality embryos in the ICSI cycles was significantly higher than in the IVF cycles, possibly due to more successful selection of the embryo for embryo transfer on day 2 after ICSI. In addition, our data suggest that embryo quality is a more important determinant of outcome than the age of the woman.