Endocrinology: A prospective randomized single-blind comparative trial of nafarelin acetate with buserelin in long-protocol gonadotrophin-releasing hormone analogue controlled in-vitro fertilization cycles

The use of gonadotrophin-releasing hormone (GnRH) agonists tocontrol ovulation induction cycles for in-vitro fertilization(IVF) has been shown to increase the pregnancy rate and livebirth rate compared with non-analogue cycles. Different formulationsof GnRH agonist are available with different routes and frequenciesof administration. In this prospective study, the efficacy andsafety of intranasal nafarelin and buserelin as adjunctive therapyduring IVF were assessed. A total of 240 female patients wererecruited to the study and in the first phase patients wererandomized to receive either intranasal nafarelin 200 µgtwice daily or buserelin 200 µg five times daily. In thesecond phase, patients received either nafarelin 400 µgtwice daily or buserelin 200 µg five times daily. Nafarelin400 µg and buserelin 200 µg both produced clinicalpregnancy rates of 31% per recruit and 39% per embryo transfer.The rates for nafarelin 200 ug were 23 and 37% respectively.There was no statistically significant difference in pregnancyrates, by either drug or dosage. The time taken for pituitarydown-regulation to be achieved was significantly longer on nafarelin200 µg than on either nafarelin 400 µg or buserelin.The total number of days stimulation with human menopausal gonadotrophinrequired to reach criteria for human chorionic gonadotrophin(HCG) administration was significantly longer on buserelin thanon either dose of nafarelin. Median serum oestradiol concentrationson the day of HCG administration were significantly higher oneither dose of nafarelin than on buserelin.     

Embryo quality and uterine receptivity in in-vitro fertilization cycles with or without agonists of gonadotrophin-releasing hormone

The proportion of abnormal oocytes or embryos per recovered oocyte in in-vitro fertilization (IVF) cycles had no influence on the occurrence of pregnancy following the transfer of normal embryo(s) derived from oocytes capable of fertilization. There were more implantations per transferred embryo in stimulated IVF cycles using long-acting buserelin (30.0%) compared with short-acting decapeptyl (17.3%) or no gonadotrophin-releasing hormone agonist (GnRHa, 15.2%) treatments. However, the chances of implantation per embryo transferred being in excess of one in patients who became pregnant tended to be higher in non-GnRHa (23.5%) compared to buserelin- (16.4%) or decapeptyl- (13.3%) treated IVF cycles. Moreover, frozen--thawed embryos had a higher implantation rate (P less than 0.05) when originating from IVF cycles without GnRHa (11.7%) compared to GnRHa-treated cycles (buserelin, 4.3%; decapeptyl, 5.9%). It can be concluded that GnRHa associated with gonadotrophins produced embryos of a poorer aptitude for development than stimulation treatments without GnRHa. The clinical efficacy of GnRHa in IVF--ET cycles could be the result of an improved uterine receptivity to the transferred embryos.     

A prospective randomized comparison of two gonadotrophin-releasing hormone agonists, nafarelin acetate and buserelin acetate, in in-vitro fertilization-embryo transfer

We tested the efficacy of a new gonadotrophin-releasing hormoneagonist (GnRHa), nafarelin acetate, in in-vitro fertilization(IVF), and compared the results with those of another widelyused GnRHa, buserelin acetate; both were in the form of nasalspray. Therapy was used in a long protocol in the luteal phasein two groups of women with similar aetiology of infertility.There was no significant difference in patient response, measuredby cycle cancellation, number of oocytes retrieved, fertilizationrate and cleavage rate. Pregnancy rates were similar in nafarelinacetate and buserelin acetate treated women, namely 22% and24% pregnancies per cycle, and 28.8% and 32.1% pregnancies pertransfer, respectively. Side-effects were few and comparablein both groups. The only difference noted was that women receivingnafarelin acetate required significantly fewer ampoules of humanmenopausal gonadotrophin, making a significant difference inthe expense involved. We conclude that on the basis of our experience,nafarelin acetate is an efficient and safe gonadotrophin-releasinghormone agonist, effective in IVF therapy     

Dose-finding study for the use of long-acting gonadotrophin-releasing hormone analogues prior to ovarian stimulation for IVF

Gonadotrophin-releasing hormone (GnRH) analogues improve the outcome of treatment with IVF by increasing the number and quality of oocytes retrieved and by reducing cycle cancellation rates. Whilst short-acting GnRH analogues are most commonly used, depot preparations are now available that are more convenient for patient use. Some studies have reported that pregnancy rates with depot GnRH analogues are similar to those of short-acting preparations, but others have suggested that the more profound down-regulation seen with depot GnRH analogues results in inferior embryo quality. The purpose of this study was to determine whether a lower than conventional dose of a depot GnRH analogue may be more appropriate for use in ovarian stimulation prior to IVF. Sixty patients were randomized to receive either 3.75 mg (conventional dose) or 1.87 mg (low dose) triptorelin prior to ovarian stimulation for IVF. Suppression was measured using serum concentrations of LH measured 2 and 3 weeks after the administration of the GnRH analogues, the dose of gonadotrophin used and the time to resumption of menses. Mean concentrations of LH were 2.2 +/- 1.0 and 1.1 +/- 0.6 IU/l in the conventional dose group and 3.5 +/- 5.5 and 2.7 +/- 1.9 IU/l in the low dose group (P < 0.05 at 2 and 3 weeks). There were no significant differences between the doses of gonadotrophins used, the number of oocytes and embryos available and the time to resumption of menses, nor in the pregnancy rates. Although the degree of suppression as measured biochemically was more profound with the conventional dose, this did not affect the IVF outcome. The use of a lower dose therefore appears to be equally effective and could contribute to a reduction in the cost of treatment.     

Combination of long and short term GnRH analogue protocols: a new therapeutic approach to persistent high progesterone levels in IVF cycles.

Thirty-four patients who had had persistently high progesterone (P) levels during menotrophin therapy in previous in-vitro fertilization (IVF) cycles, despite pretreatment with a long acting gonadotrophin-releasing hormone analogue (GnRHa), were randomly divided into two groups according to the mode of ovulation induction used. In 16 women (group 1), induction of ovulation was performed with decapeptyl (DTRP6)/pure follicle-stimulating hormone (PFSH)/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG). In 18 patients (group II), the protocol was identical to the former group, except for the addition of a short-acting GnRHa (buserelin) that was started when P levels were persistently high. The combination of long and short acting GnRH analogues (group II) resulted in an improved follicular phase with significantly lower P levels on the day of HCG administration (P less than 0.001). Furthermore, a significantly higher number of oocytes was retrieved, fertilized and cleaved (P less than 0.005; P less than 0.001; P less than 0.005, respectively) and, as a consequence, significantly higher pregnancy rates were achieved (22.2 versus 12.5%; P less than 0.005). These results indicate that a combination of long- and short-acting GnRH agonists may be of value in cases of persistent high P levels during menotrophin therapy in IVF cycles. Further larger studies must be performed before the true efficacy of this mode of treatment can be determined.     

The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone

Luteal support is essential in in-vitro fertilization (IVF)when long-acting gonadotrophin-releasing hormone agonist (GnRHa)is used. Because progesterone lacks luteotrophic stimulation,it seems to be the drug of choice in cases with an increasedrisk of ovarian hyperstimulation syndrome (OHSS). The aim ofthis study was to assess the beneficial effect of the mid-lutealaddition of human choriomc gonadotrophin (HCG) in IVF, usinga down-regulation protocol and luteal support with progesterone,in a prospective randomized study. The study included 170 IVFcycles down-regulated with long-acting GnRHa which were supportedwith 50 mg/day progesterone i.m. during the luteal phase. Patientswere evaluated in the mid-luteal period. Those without clinicalsigns of OHSS, oestradiol concentrations <1000 pg/ml andprogesterone concentrations <50 mg/ml were randomly allocatedto either the addition of 2500 IU HCG (HCG+ group) or no HCG(HCG– group). End luteal phase progesterone concentrationsamong non-pregnant patients were used to assess the contributionof exogenous progesterone and to categorize pregnancies accordingto their corpus luteum function. Similar low OHSS (2.7 and 1.8%)and pregnancy (30 and 29%) rates were observed in the HCG+ andHCG– groups respectively. Of the 26 pregnancies in theHCG+ cases, there was only one case with reduced corpus luteumfunction, compared with 12 of the 25 pregnancies among HCG–patients. Cases with reduced corpus luteum function requiredcontinuous progesterone support and presented lower HCG concentrationsand a higher rate of adverse pregnancy outcome. We concludethat mid-luteal HCG addition does not affect pregnancy rate,but in fact helps to preserve corpus luteum function and avoidsthe need for further supplementation during early pregnancy.     

Endometriosis: Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis

The objective of our study was to establish the most adequateovarian stimulation regimen for assisted procreation in endometrioticpatients. It consisted of a retrospective analysis comparingthe use of the gonadotrophin-releasing hormone analogue (GnRHa)buserelin either for 3 months or for 3 weeks and continued withovarian stimulation with human menopausal gonadotrophin (HMG),and the use of clomiphene citrate in association with HMG forin-vitro fertilization (IVF) and embryo transfer, gamete intra-Fallopiantransfer (GIFT) and zygote intra-Fallopian transfer (ZIFT).A total of 145 patients with endometriosis in 174 cycles weredivided into two groups according to the revised American FertilitySociety staging of the disease (group A, stages 1 and 2; groupB, stages 3 and 4). The use of GnRHa significantly increasedthe number of oocytes retrieved. GnRH analogues for 3 monthsgave the highest fertilization rate for groups A and B. Thecleavage, pregnancy and delivery rates, although higher in thegroups treated with analogues, did not reach statistical significance.A higher number of patients had an embryo transfer in the groupstreated with GnRHa (P < 0.05). Treatment with GnRHa for either3 months or for 3 weeks proved to be more efficient than clomiphenecitrate-HMG for assisted procreation procedures in patientswith endometriosis.     

Normal pregnancy outcome after inadvertent exposure to long-acting gonadotrophin-releasing hormone agonist in early pregnancy.

Five infertile women exposed to long-acting gonadotrophin-releasing hormone agonist (GnRHa) during early pregnancy were studied to assess the risks of embryotoxicity on the outcome of their pregnancies. All the patients were diagnosed as stage 3-4 endometriosis following laparoscopy. Long-acting GnRHa (3.75 mg) was given in the first 3 days of their preceding menstrual period. Four of the five patients had two GnRHa injections and the last patient had three GnRHa injections. All patients were advised to use a barrier contraception (condoms) throughout the treatment period. Since all complained of no bleeding following the initial injections, human chorionic gonadotrophin (beta-HCG) concentrations were tested in order to rule out any pregnancy. Ultrasonographic examinations were commenced routinely and all patients had amniocentesis at 16-18 weeks gestational age. Genetic analysis revealed a normal karyotype in all fetuses. All five pregnancies progressed to term without complication, and normal healthy infants were delivered. Although there are still no clear answers concerning teratogenic and hormonal effects of GnRHa exposure in pregnancy, our data may suggest that luteal function, genetic structure and pregnancy outcome are not adversely affected by GnRHa. Since possible subtle effects on fetal endocrine organs cannot be disregarded, close monitoring is still needed in GnRHa-exposed pregnancies.     

Endocrinology: Outcome of inadvertent administration of a gonadotrophin-releasing hormone agonist (buserelin) in early pregnancy

All women undergoing pituitary down-regulation before plannedin-vitro fertilization (IVF) treatment in two IVF units werestudied to assess the risks of and to pregnancies occurringinadvertently when gonadotrophin-releasing hormone agonists(GnRHa) were used to achieve pituitary desensitization duringthe luteal phase prior to planned IVF treatment. In 2670 cycles,25 women conceived (0.9% of cycles). Of these, three resultedin pre-clinical abortions (12%) but there were no clinical abortions,and 22 have ended with live births at term of apparently normalinfants. Collation of these and other published data suggestthat pregnancy outcome is not adversely affected by GnRHa administrationin the luteal phase of the conception cycle.     

Addition of estradiol to progesterone for luteal supplementation in patients stimulated with GnRH antagonist/rFSH for IVF: a randomized controlled trial

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.     

Inadvertent gonadotrophin-releasing hormone agonist (GnRHa) administration in the luteal phase may improve fecundity in in-vitro fertilization patients

Spontaneous pregnancies associated with inadvertent periconceptionaladministration of a gonadotrophin-releasing hormone agonist(GnRHa) oocur in 1% of in-vitro fertilization (IVF) cycles.The two main issues to be considered in these circumstancesare the luteolytic effect of the agonist and embyrotoxicity.In addition, some authors have suggested a higher incidenceof ectopic implantations. In view of these concerns, we reporton 15 patients who conceived during pituitary desensitizationwith a GnRHa in the luteal phase of the menstrual cycle, andreview the literature on the subject. A detailed analysis ofthe data available so far, which include 59 pregnancies exposedto GnRHa, shows that: (i) there is no clinical evidence forimpaired luteal function, and hormonal supplementation doesnot improve pregnancy outcome; (ii) with only two cases of reportedminor malformations among 37 deliveries, both having a geneticcomponent, there is no evidence of teratogenic effects; and(iii) ectopic implantations in these circumstances are relatedto tubal disease but not to the drug. Considering the long historyof infertility in these patients who had previously been treatedunsuccessfully by different therapeutic modalities, it is likelythat the occurrence of those pregnancies is not merely coincidentaland that GnRHa might have a positive role in fecundity. Theimproved fecundity may be explained by the mechanisms of luteinizinghormone action in the corpus luteum.     

Hormonal and histological evaluation of the luteal phase after combined GnRH-agonist/gonadotrophin treatment for superovulation and luteal phase support in in-vitro fertilization.

A hormonal and histological study of the luteal phase was performed in 21 stimulated in-vitro fertilization (IVF) patients not undergoing embryo transfer. Ovarian stimulation was carried out with gonadotrophins [follicle stimulating hormone (FSH) + human menopausal gonadotrophin (HMG)] under pituitary suppression with buserelin. Ovulation was induced with 5000 IU human chorionic gonadotrophin (HCG) and additional doses of 5000, 2500 and 2500 IU were given on the day of follicular aspiration, and 2 and 5 days later respectively, to support the luteal phase. Supraphysiological levels of oestradiol (E2) and progesterone in plasma were found in the midluteal phase of all women, while prolactin was in the normal range. An endometrial biopsy taken in the late luteal phase was normal in 90.5% (19/21) of patients, most of them (15/19, 79%) having E2 greater than 1500 pg/ml on the day of HCG. Conversely, both patients with defective endometrial biopsies had E2 levels less than 1500 pg/ml.     

Depot versus daily administration of GnRH agonist protocols for pituitary desensitization in assisted reproduction cycles: a Cochrane Review

This paper is based on a Cochrane review published in The Cochrane Library, issue 4, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration. 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. BACKGROUND: GnRH agonists have been widely used in cycles of IVF. There are two types of GnRH agonist administration that can be used to lead to hypophysis desensitization in IVF cycles in the long protocol: one consisting of daily low doses of GnRH agonist and the other the administration of analogues in higher, long-acting doses (depot). The objective of this study is to compare the use of a single long-acting depot dose with that of daily GnRH agonist doses in IVF cycles. METHODS: Relevant randomized controlled trials were identified by electronic search of the following databases: MEDLINE, EMBASE, LILACS (Latin American and Caribbean Center on Health Sciences Information) and the Cochrane Controlled Trials Register. Six studies, with a total of 552 women, were included and analysed. RESULTS: The studies do not indicate that there is a statistically significant difference between the use of depot GnRH agonist and of daily GnRH agonist in the primary outcome, clinical pregnancy rates per woman [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.65-1.37]. However, there was sufficient evidence showing that the use of depot GnRH agonist for pituitary desensitization in IVF cycles increased the number of gonadotrophin ampoules [weighted mean difference (WMD) 3.30, 95% CI 1.27-5.34] and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31-0.81), as compared with the use of daily GnRH agonist. CONCLUSIONS: Although we recognize that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocols using depot or daily GnRH agonist for IVF cycles. However, the use of depot GnRH agonist is associated with increased requirements for gonadotrophins and a longer time needed for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRH agonist would increase the overall costs of IVF treatment.     

Serum inhibin levels in gonadotrophin stimulated in-vitro fertilization/gamete intra-fallopian transfer cycles.

Serum inhibin concentrations of 64 cycles of in-vitro fertilization--embryo transfer (IVF-ET) or gamete intra-Fallopian transfer (GIFT) have been analysed retrospectively. No significant difference was observed in serum inhibin levels of cycles stimulated with buserelin and human menopausal gonadotrophin (HMG) or HMG alone. During the late follicular phase, serum inhibin was higher in cycles resulting in pregnancy than in cycles without a pregnancy (peak values on day +1: 8.3 versus 6.4 IU/ml, respectively). The same difference was found between stimulation cycles resulting in a viable or a non-viable pregnancy (peak values on day +1: 8.3 versus 7.5 IU/ml). However, these differences were not significant. During the early luteal phase, serum inhibin values were similar in these groups of patients. Our results indicate that the use of the gonadotrophin-releasing hormone (GnRH) analogue buserelin, in combination with HMG, for ovarian stimulation does not affect inhibin production by granulosa cells in vivo. The late follicular and early luteal concentrations of serum inhibin have to be considered unsuitable as predictors in IVF/GIFT cycles with respect to pregnancy and pregnancy outcome.     

Gonadotrophin-releasing hormone agonist compared with human chorionic gonadotrophin for ovulation induction after clomiphene citrate treatment

The objective of this study was to compare hormonal response,luteal phase adequacy and pregnancy and abortion rates in patientsrandomized to receive human chorionic gonadotrophin (HCG) orgonadotrophinreleasing hormone agonist (GnRHa) during ovulationcycles stimulated by clomiphene citrate. Anovulatory patientsreceived either one s.c. dose of tryptorelin (0.1 mg; n = 104)or one i.m. dose of HCG (10 000 IU; n = 106) after clomiphenecitrate stimulation had induced enlarged ovarian follicles (>17mm in diameter). A short-lived, transitory increase in serumluteinizing hormone (98 ± 9 IU/1) and follicle-stimulatinghormone (30 ± 5 IU/1) concentrations was measured at12 h following the injection of GnRHa, and these concentrationsreturned to baseline levels by 36 h post-injection. Midlutealprogesterone concentrations were similar in both groups (>10ng/ml), and the mean luteal phase duration was also not significantlydifferent (13 days). There were no significant differences inthe mean number of pregnancies (12.0 versus 12.6% per cycle)and the abortion rate (18.2 versus 12.5%) between the GnRHa-and HCG-treated groups respectively. There were no complicationsrelated to treatment in either group. The results show thata relatively low dose of GnRHa can be used in place of HCG toinduce ovulation in clomiphene citrate-treated patients.     

Increased pregnancy failure rates after clomiphene following assisted reproductive technology.

The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra-Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols. Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF and GIFT data were considered separately. However, the abortion rate for combined IVF and GIFT was significantly higher after clomiphene than after GnRHa. This pattern was found for most maternal age groups and causes of infertility although differences were not significant in all categories. The combined IVF and GIFT ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1% for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment during folliculogenesis means that GnRHa cannot be used with clomiphene, luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa cycles. Clomiphene itself could cause the increase in pregnancy wastage or increased levels of LH during follicule genesis associated with the use of clomiphene may cause the observed pregnancy failures.     

An improved use of buserelin in ovarian stimulation for in-vitro fertilization

In earlier IVF programmes, subcutaneous buserelin (Suprefact, Hoechst) was initially administered three times per day (200 micrograms x 3); then twice daily (300 micrograms x 2). We now suggest that a single administration of 600 micrograms daily may be equally effective. In a preliminary study, 20 patients were selected on the basis of tubal or idiopathic infertility and received 0.6 ml buserelin subcutaneously once a day, beginning on day 1 or 2 of the cycle. A sufficient pituitary desensitization was obtained on day 10 in 75% of patients and on day 16 for 100% and the ongoing pregnancy rate was 35% per treatment cycle. A randomized study comparing the effect of 600 micrograms of buserelin administered in one (n = 50) or two injections (n = 46), has been carried out and indicates that the results in terms of the ovarian suppression and pregnancy rates, were similar. Therefore, this protocol represents a simplification of the treatment with buserelin.     

Endocrinology: Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization

The present study was undertaken to assess whether the increasein serum progesterone concentration following the administrationof human chorionic gonadotrophin (HCG) may have predictive valueon the in-vitro fertilization (IVF) success rate. Progesteroneconcentration on the day of HCG administration and the increasein progesterone concentration on the following day were evaluatedin 140 consecutive patients undergoing IVF with embryo transfer.Stimulation protocol in all study patients entailed intranasaladministration of short-acting gonadotrophin-releasing hormoneagonist (GnRHa) buserelin and human menopausal gonadotrophin.A pregnancy rate of 37.2% was achieved when at least three embryoswere transferred. The only significant difference between conceptionand non-conception cycles was found in serum progesterone concentrationsafter HCG administration (P < 0.01), whereas the mean progesteroneconcentration on the day of HCG did not differ. No differencein other hormonal or cycle parameters was observed. The increasein progesterone concentration was significantly greater in thegroup of patients who achieved pregnancy than in the group whodid not (2.2 ± 0.2 versus 1.6 ± 0.1 ng/ml, respectively;P < 0.01). A critical breakpoint in serum progesterone wasarbitrarily determined at 1 ng/ml. An increase in progesteroneconcentration 1 ng/ml when three or more embryos were transferredwas associated with a positive predictive value for pregnancyof 40.4% (sensitivity of 94.7%), whereas a negative predictivevalue of 86.7% was obtained when this value was <1 ng/ml.These findings indicate that an adequate rise in serum progesteronefollowing HCG administration provides useful information aboutthe possible outcome of the treated cycle.     

Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization

Gonadotrophin-releasing hormone agonists (GnRHa) are widely used in in-vitro fertilization (IVF) for the prevention of a premature rise in luteinizing hormone (LH) concentrations. However, the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion. Therefore, luteal supplementation is generally applied. The present study was designed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum. Sixty patients were randomized for three groups: (i) A long GnRHa/human menopausal gonadotrophin (HMG) protocol with luteal support by repeated human chorionic gonadotrophin (HCG) (n = 20), (ii) early follicular phase cessation of GnRHa without luteal support (n = 20), and (iii) a long GnRHa protocol without luteal support (n = 20). Frequent ultrasound and blood sampling was performed during the entire IVF cycle. Forty normo-ovulatory women served as controls. No premature LH surges were found after early cessation of GnRHa. In this group, some pituitary recovery occurred during the late luteal phase, but this did not affect corpus luteum function. Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG. Pregnancies occurred in all three groups. In conclusion, early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH. Although some pituitary recovery was observed thereafter, corpus luteum function is still abnormal due to early luteolysis.     

A prospective randomized trial of human chorionic gonadotrophin or dydrogesterone support following in-vitro fertilization and embryo transfer

A randomized, prospective blind study was carried out to investigate the need for luteal phase support in patients undergoing in-vitro fertilization (IVF). One-hundred-and-fifty-six patients undergoing IVF in cycles stimulated with human menopausal gonadotropin (HMG) and human chorionic gonadotrophin (HCG) stimulated IVF, were divided into three different groups for luteal phase treatment. Fifty-four patients received dydrogesterone three times daily (TID) beginning on the day of embryo transfer (ET). Fifty-one patients received HCG on days 3, 6 and 10 following ET. Fifty-one patients received placebo p.o. TID beginning on the day of ET. There was no difference between the groups in pregnancy rate, rate of spontaneous abortion, proportion of normally developing fetuses or rate of chemical pregnancy. The data indicate that supplementation of the luteal phase may not improve the success rates of IVF-ET cycles.