The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

It has been suggested that the luteinizing hormone (LH) activityof human menopausal gonadotrophin (HMG) preparations used forovarian stimulation in in-vitro fertilization (IVF) may haveadverse effects on reproductive outcome. In the present prospective,randomized trial of 218 infertile couples this notion was investigated.A total of 114 women were treated with Pergonal (HMG group)and 104 with Fertinorm HP (HP-FSH group). The two groups werecomparable with regard to duration of infertility, cause ofinfertility, age and number of previous IVF attempts and allhad normal basal gonadotrophin concentrations before treatmentwas started. A standard hormonal treatment consisting of pituitarydown-regulation with gonadotrophin-releasing hormone analogue(GnRHa) for 14 days starting on cycle day 21, followed by eitherHMG or highly purified follicle stimulating hormone (HP-FSH),three ampoules (225 IU) per day for 7 days, was used in allcases. The daily hormone dose was thereafter individualizedaccording to the ovarian response. A maximum of two pre-embryoswere transferred after 3 days of culture. Luteal support withprogesterone (300 mg per day intravaginally) was used in allcases. Serum concentrations of oestradiol, FSH and LH were measuredon days 1 and 8 of stimulation and on the day of oocyte retrieval.The mean number of days of stimulation, mean number of ampoulesof HMG or HP-FSH used, mean total motile sperm count on theday of oocyte retrieval and mean numbers of oocytes retrieved(13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8)were similar for both groups. Significantly (P < 0.05) morecycles in the HP-FSH group (17 = 16%) were cancelled due tocomplete failure of fertilization than in the HMG group (7 =6%). The mean fertilization rate was significantly (P < 0.05)higher in the HMG group (56%) than in the HP-FSH group (50%),and significantly more transferable pre-embryos were obtainedin the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P< 0.01). Serum hormone concentrations were similar in thetwo groups on stimulation day 1, but differed significantlywith regard to FSH, LH and oestradiol on stimulation day 8.The clinical outcome was similar in the two groups, with anongoing pregnancy rate (>12 weeks of gestation) per startedcycle of 33% in the HMG group and 29% in the HP-FSH group. Theclinical abortion rates were similar(10 and 14%), and the implantationrate was 30% in each group. In conclusion, no detrimental effectof the LH activity of HMG on the clinical outcome of IVF inGnRHa down-regulated normogonadotrophic women was found. Tothe contrary, some beneficial effects of HMG on fertilizationrates and pre-embryo development as compared with HP-FSH weredemonstrated. These effects, as well as the differences in serumhormone concentrations during ovarian stimulation, may be causedby differences in LH content and/or in the composition of FSHisoforms of the HMG and HP-FSH preparations.     

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization*

The adverse effect of raised luteinizing hormone (LH) concentrationson reproductive outcome suggests that exogenous LH administrationfor ovarian stimulation may not be desirable. The aim of thisstudy was to compare the clinical pregnancy rates between folliclestimulating hormone (FSH) and human menopausal gonadotrophin(HMG) used in in-vitro fertilization (IVF) cycles. A total of232 infertile patients, with a mean duration of infertilityof 67.1 ± 32.9 months, were selected for IVF (femaleage <38 years, FSH <15 IU/1, and total motile sperm count>5x10⁶). A short (flare-up) protocol with daily leuprolideacetate was followed randomly from day 3 with FSH (n = 115)or human menopausal gonadotrophin (HMG; n = 117), at an initialdose of two ampoules per day. A maximum of three embryos wastransferred, and the luteal phase was supported with four dosesof HCG (2500 IU). No differences were observed between the twogroups in any of the cycle response variables except fertilizationrates per oocyte and per patient, both of which were significantlyhigher with FSH. Clinical pregnancy rates per cycle initiated,per oocyte retrieval and per embryo transfer were 19.1, 21.0and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectivelyfor HMG. Whilst these differences were not statistically significant,the results of this interim analysis suggest that HMG may beassociated with a lower clinical pregnancy rate than FSH.     

Recombinant follicle stimulating hormone is effective in poor responders to highly purified follicle stimulating hormone

Ovarian stimulation in cases of poor ovarian responsiveness is an important challenge in in-vitro fertilization (IVF) programmes. Despite improvements in oocyte number and quality, an ideal ovarian stimulation strategy has yet to be defined. Here, the results of ovarian stimulation with recombinant follicle stimulating hormone (rFSH) in 28 poor responders to highly purified FSH (FSH-HP) with high basal concentrations of FSH are reported. The protocols used on the FSH-HP and rFSH cycles were identical with the sole exception of the FSH preparation: triptorelin 0.1 mg/day (gonadotrophin-releasing hormone, GnRH-agonist short protocol) and the starting FSH dose of 300 IU/day were administered from day 2 of the menstrual cycle. Ovarian outcome was classified as 'normal', 'intermediate' and 'poor', depending on the number of mature oocytes retrieved and the peak serum oestradiol concentration. Nine of the 28 subjects had an intermediate ovarian response to re-stimulation with rFSH. In the 26 patients who received human chorionic gonadotrophin on both cycles, re-stimulation resulted in a significant increase (P < 0.05) in the mean number of mature oocytes (2.4 +/- 1.4 versus 1.7 +/- 0.8), mean peak oestradiol concentration (606 +/- 252 versus 443 +/- 32 pg/ml) and fertilization rate (73.0 versus 53.3%). Four pregnancies were achieved. It is concluded that rFSH in a GnRH-agonist short protocol improves the ovarian outcome in poor responders to FSH-HP with high basal concentrations of FSH.     

Ovarian stromal blood flow in the prediction of ovarian response during in vitro fertilization treatment

BACKGROUND: This study evaluated the role of ovarian stromal blood flow in the prediction of the ovarian response of infertile women by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal blood flow indices measured by power Doppler in two-dimensional ultrasound. Patients were aged <40 years with basal FSH <10 IU/l on recruitment for IVF treatment. METHODS: All received a standard regimen of ovarian stimulation in their first IVF cycle. AFC, pulsatility index, resistance index and peak systolic blood flow velocity of ovarian stromal vessels were determined on the second day of the treatment cycle prior to ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, and the duration and dosage of gonadotrophins. RESULTS: A total of 136 women were included in the analysis. Basal FSH concentration achieved the best predictive value in relation to the number of oocytes obtained, followed by AFC and BMI. AFC was the only predictive factor of serum oestradiol concentration on the day of HCG while BMI was predictive of the gonadotrophin dosage. CONCLUSION: Ovarian stromal blood flow indices measured by power Doppler ultrasound had no predictive value for the ovarian response.     

Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles

In order to assess the efficacy and safety of recombinant humanfollicle stimulating hormone (FSH) in routine clinical use,ovarian stimulation with recombinant human FSH was performedin 71 patients prior to in-vitro fertilization (IVF) withoutgonadotrophin-releasing hormone (GnRH) analogues in a multicentre,non-comparative study. Human chorionic gonadotrophin (HCG) wasadministered to 58 patients (81.7%), 15 of whom underwent 19cycles with an initial dosage of three ampoules daily of recombinantFSH and 43 of whom underwent 152 cycles with four ampoules dailyfrom day 3 onwards. No significant differences were detectedbetween these two groups in all test parameters. The mean durationof treatment was 9.06 and 8.86 days respectively with a meannumber of 24.06 and 23.25 vials of recombinant human FSH administered.A mean number of 6.26 and 5.88 oocytes respectively was collected.The number of transferred embryos was 2.4 and 2.2. A clinicalpregnancy rate of 23.8% (10 out of 42) per transfer was achieved(30.9 and 20.6% respectively). Local tolerance of s.c. administrationwas excellent. Mild pain at the injection site was the dominantfinding in <20% of patients. Two cases of ovarian hyperstimulationsyndrome were noted. Recombinant human FSH is very attractiveto patients because it can be self-administered s.c. and thepreparation does not come from a human source. In conclusion,these data support the safety and efficacy of recombinant humanFSH in routine use for IVF.     

Endocrinology: The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone

To evaluate the relative importance of follicle stimulatinghormone (FSH) and luteinizing hormone (LH) in follicular developmentand oocyte fertility in the human species, the use of recombinanthuman FSH, human menopausal gonadotrophin (HMG), and very highlypurified urinary human FSH (FSH-HP) plus oestradiol valeratefor ovarian stimulation and in-vitro fertilization (IVF) werecompared in three cycles in a woman with isolated congenitalgonadotrophin deficiency who had never been treated with ovarianstimulating agents. The total number of ampoules of gonadotrophinsused was lower in the HMG treatment cycle. Ovarian responseand IVF outcome in the three treatment cycles were as follows:(i) HMG cycle: normal follicular growth, normal pattern of oestradioland inhibin through the menstrual cycle, high fertilizationrate (93%); (ii) recombinant FSH cycle: normal follicular growth,low oestradiol and abnormal inhibin, finally poor rate of fertilization(28%); (iii) FSH-HP plus oestradiol valerate cycle: normal folliculargrowth, normal pattern of inhibin and poor fertilization rate(27%). Luteal plasma progesterone concentrations were much higherin the HMG treatment cycle. This case shows that FSH is theonly factor required in order to induce follicular growth inthe human, although LH or a product derived from its actionmay assist in order to achieve full follicular maturity andoocytes capable of fertilization. Though oestradiol might havea mediatory role in the process of follicular maturation, ourresults favour a direct primary role of LH in complete maturationof the follicle.     

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH- stimulated patients.      

Endocrinology: Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotrophin-releasing hormone antagonist-treated monkeys

Both follicle stimulating hormone (FSH) and luteinizing hormone(LH) are proposed requirements for follicular growth and steroidogenesis;however, the role of LH in primate folliculogenesis is unclear.Follicular stimulation by recombinant human FSH (n = 5) withand without recombinant LH (1: 1; n = 6) following 90 days ofgonadotrophin-releasing hormone (GnRH) antagonist (Antide) treatmentin macaques was evaluated. Human chorionic gonadotrophin (HCG)was administered when six follicles >4 mm were observed.Oocytes were aspirated 27 h later and inseminated in vitro.Chronic Antide reduced serum oestradiol and bioactive LH toconcentrations observed in hypophysectomized rhesus monkeys.Multiple follicular growth required a longer interval followingrecombinant FSH (12 ± 1 days) than recombinant FSH +recombinant LH (9 ± 0.2 days), but the total number offollicles/animal did not differ between groups. The day priorto HCG, oestradiol concentrations were 4-fold less followingrecombinant FSH compared to recombinant FSH + recombinant LH.With recombinant FSH, more oocytes completed meiosis to metaphaseII(51%) and fertilized (89 ± 5%) relative to recombinantFSH + recombinant LH (12 and 52 ± 11% respectively).Follicular growth and maturation in LH-deficient macaques occurredwith FSH alone. Thus, LH is not required for folliculogenesisin primates. Higher fertilization rates following follicularstimulation with FSH alone suggest that the presence of LH withFSH (1: 1) during the pre-ovulatory interval impairs gametogenicevents in the periovulatory period.     

Endocrinology: Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation

The aim of the present study was to investigate whether reducingthe amount of luteinizing hormone (LH) in gonadotrophic preparationsimpairs follicular growth in in-vitro fertilization (IVF) cyclesduring suppression of endogenous LH levels. A selected groupof 20 IVF patients was randomly divided into two groups. Onegroup was treated with Org 31338 [follicle stimulating hormone(FSH)/LH 3: 1], the other group with Metrodin® (purifiedFSH), both during pituitary down-regulation with buserelin.A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrationsof FSH, LH, oestradiol and progesterone were determined frequentlyand serial ultrasound examinations were performed. Multiplefollicular growth with concomitant rise of oestradiol levelswas observed in all cycles. The duration of the stimulationphase was shorter in the group treated with Org 31338 than inthe group treated with Metrodin. The number of follicles andoocytes and the fertilization rate was larger and the mean embryoquality was higher in the Org 31338 group, but the differencesdid not reach statistical significance. No significant differenceswere found in hormonal values. In women with normal endocrineprofiles, lowering of the LH activity in gonadotrophic preparationsduring gonadotrophin-releasing hormone agonist treatment resultsin adequate ovarian stimulation. However, a preparation withsome LH needed a shorter stimulation than a purified FSH preparation.Whether the other beneficial effects of Org 31338 also occurin a larger population needs further investigation.     

Reducing the dose of gonadotrophin-releasing hormone agonist on starting ovarian stimulation: effect on ovarian response and in-vitro fertilization outcome

The aim of this study was to examine if lowering the dose of gonadotrophin-releasing hormone agonist (GnRHa) on starting ovarian stimulation could be beneficial in in-vitro fertilization (IVF) programmes. A total of 64 normally ovulating patients entering an IVF programme were randomized to receive GnRHa (nafarelin acetate/Synarel) as an intranasal spray commencing in the midluteal phase, either at a dosage of 200 microg three times daily until the day of human chorionic gonadotrophin (HCG) administration, or to be reduced to 200 microg twice daily as ovarian stimulation was initiated. Patients in both groups were below 35 years with a body mass index below 30. All patients received three ampoules of Metrodin HP per day. Blood samples were taken on the day of HCG administration to measure luteinizing hormone (LH), oestradiol, and progesterone. LH and oestradiol were found to be significantly higher in the lower Synarel dose group. Our results show that reducing the GnRHa dose during ovarian stimulation in IVF might be beneficial in terms of significantly more oocytes recovered, and significantly greater number of embryos available for transfer and freezing, with no incidence of premature luteinization.      

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.     

Ovarian volume may predict assisted reproductive outcomes better than follicle stimulating hormone concentration on day 3.

This study was undertaken to compare ovarian volume with other factors which are important for the success of assisted reproduction. The first treatment cycle for 261 patients meeting all entry criteria between September 1993 and June 1995 was considered. All cycles employed the same stimulation protocol and no interventions were based upon pre-treatment indicators. Pre-treatment ovarian volumes, cycle day 3 follicle stimulating hormone (FSH) and oestradiol concentrations, smoking status and age were compared to subsequent peak oestradiol concentrations, numbers of oocytes retrieved, cycle cancellation and occurrence of clinical pregnancy. Statistical evaluation was performed using simple and multiple logistic regression analysis to determine odds ratios. The resultant odds ratios suggest that age and small ovarian volume may predict retrieval of fewer mature oocytes, while the failure to achieve clinical pregnancy was predicted by current smoking and small ovarian volume. Day 3 FSH values failed to be a significant predictor when maternal age, smoking status and ovarian volume were known. It can be concluded that, like maternal age and smoking status, ovarian volume may be a clinically important predictor of reproductive success, being superior to cycle day 3 FSH or oestradiol concentrations as an assessment of ovarian reserve.     

Endocrinology: Influence of serum follicle stimulating hormone to luteinizing hormone ratio during buserelin acetate-induced pituitary desensitizafion on ovarian response to exogenous gonadotrophins in an in-vitro fertilization and embryo transfer programme

We investigated the effect of endogenous gonadotrophins duringpituitary desensitization with gonadotrophin-releasing hormoneagonist (GnRHa) on ovarian responsiveness or the outcome ofin-vitro fertilization (IVF) and embryo transfer. The resultsof 67 women who participated in the IVF programme at NagasakiUniversity Hospital, Japan, were analysed retrospectively. Allwomen received GnRHa from the third day of the menstrual cycle,and ovarian stimulation with exogenous gonadotrophins was initiatedwhen the serum oestradiol concentration decreased to <30pg/ml. The serum follicle stimulating hormone (FSH)/luteinizinghormone (LH) ratio, rather than serum FSH or LH concentrationsduring GnRHa-induced pituitary desensitization, showed a significantpositive correlation with age and the total dose of exogenousgonadotrophins. The FSH/LH ratio also showed a significant negativecorrelation with oestradiol response and the number of retrievedoocytes, and was significantly lower in pregnant women comparedwith the non-pregnant group during pituitary desensitization.Our results indicate that, even under pituitary desensitizationwith GnRHa, the serum FSH/LH ratio influences individual ovarianresponsiveness and the state of the intra-ovarlan hormonal environment.Our results suggest that the FSH/LH ratio may be a useful clinicalpredictor of the ovarian response to exogenous gonadotrophinsunder pituitary desensitization.     

Outcome from consecutive in-vitro fertilization/intracytoplasmic sperm injection attempts in the final group treated with urinary gonadotrophins and the first group treated with recombinant follicle stimulating hormone

In the absence of specific dose equivalency data, the aim of this study was to compare the clinical results during the cross-over from menopausal urinary products (human menopausal gonadotrophin; HMG) to recombinant follicle stimulating hormone (FSH) follitrophin beta (FSHr) in order to determine whether the manufacturer's recommendation for equivalence of ampoule to ampoule (50 IU FSHr:75 IU HMG) would prove clinically correct. A total of 353 consecutive in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles was studied between 1st September 1996 and mid-February 1997. This included cycles in the last 191 women receiving HMG and the first 162 taking FSHr. All were down-regulated using a gonadotrophin releasing hormone (GnRH) agonist long protocol method from day 1 of the cycle. Greater efficacy was seen in the HMG group in terms of days of stimulation required, need to increase dosage, cycle discontinuation, number of follicles punctured, the numbers of oocytes retrieved and their quality. The hormonal response to stimulation assessed by oestradiol concentrations on days 5, 8 and day of human chorionic gonadotrophin (HCG) was significantly lower in the FSHr group. The ratio of oestradiol per follicle and per oocyte was significantly lower in the FSHr group. There was a highly significant increase in cost with FSHr therapy. Clinical pregnancy rates were 14% per cycle with FSHr and 20% per cycle with HMG.      

The synergistic effects of clomiphene citrate and human menopausal gonadotrophin in the folliculogenesis of stimulated cycles as assessed by the gonadotrophin-releasing hormone antagonist Nal-Glu.

Clomiphene citrate (CC), alone or in combination with exogenous gonadotrophins, has been widely used in ovulation induction. CC promotes endogenous release of gonadotrophins, yet when used in combination with exogenous gonadotrophins, its contribution to folliculogenesis is difficult to assess. In order to determine the contribution of CC-induced endogenous gonadotrophin production to the overall ovarian stimulation in cycles treated with CC/human menopausal gonadotrophin (HMG), Nal-Glu, a gonadotrophin-releasing hormone (GnRH) antagonist was administered. Fertile women (n = 10) undergoing ovarian stimulation and oocyte aspiration for the sole purpose of gamete donation were studied. Five women received CC (100 mg daily for 5 days) in conjunction with pure follicle stimulating hormone (FSH) 150 IU daily. Five women received HMG alone. Nal-Glu (50 micrograms/kg/day) was administered intramuscularly to both groups when the leading follicles reached a mean diameter of 16 mm. Human chorionic gonadotrophin (HCG) 10,000 IU was given when the largest follicles reached a mean diameter of 20-22 mm. A significant fall in serum oestradiol levels was observed in women given CC/FSH (37.9 +/- 7.3%) within the first 24 h of Nal-Glu administration. Serum luteinizing hormone (LH) decreased greater than 20% within 24 h of Nal-Glu administration and remained low throughout the rest of the treatment. No decrease in oestradiol levels was noted in cycles receiving HMG alone. With supplemental FSH, falling oestradiol levels in CC/FSH cycles rebounded and continued to rise until the day after HCG administration. Despite a drop in oestradiol in CC/FSH cycles, the aspirated oocytes exhibited no untoward effects. The fertilization and cleavage rates were similar, and pregnancies occurred in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the need for follicle stimulating hormone in early preantral mouse follicle culture in vitro

In two consecutive controlled experiments 160 early preantral follicles were cultured in order to evaluate effects of recombinant follicle stimulating hormone (r-FSH) on survival, differentiation, oestradiol and inhibin secretion, cumulus mucification and cumulus-corona-oocyte detachment by human chorionic gonadotrophin (HCG) stimulation. Nuclear maturation in oocytes was also assessed following addition of HCG. A histological analysis of cultured follicles was carried out on semi- thin sections at various culture stages. Addition of r-FSH was essential for follicle survival for 16 days: without r-FSH only 11% of the follicles survived for 12 days (with r-FSH: 79%) and none of these mucified after the HCG stimulus. r-FSH promoted granulosa cell proliferation and antral-like cavity formation. Without r-FSH, histology of the cultures demonstrated degeneration and reduced granulosa cell proliferation; oestradiol and inhibin production were reduced. This study illustrates the essential role of FSH in promoting the in-vitro growth of early preantral mouse ovarian follicles and in maintaining the oocyte under meiotic arrest.      

Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment

The present study investigates the usefulness of inhibin A, inhibin B and serum oestradiol concentrations obtained in the fifth day of gonadotrophin therapy in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. A total of 80 women undergoing their first cycle of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproductive treatment programme matching by race, age, body mass index, and indication for IVF/ICSI to those in the cancelled group. For each cancelled cycle, three IVF/ICSI women who met the matching criteria were included. Basal follicle stimulating hormone (FSH) concentrations were significantly higher in the cancelled than in the control group, whereas basal inhibin B was significantly higher in the latter. Basal oestradiol concentrations were similar in both groups of patients. On day 5 of gonadotrophin therapy serum concentrations of oestradiol, inhibin A and inhibin B were significantly lower in the cancelled group as compared with controls. Logistic regression analysis showed that the association for day 5 inhibin B (with a predictive value of ovarian response of 91.03%) with cancellation rate was significant, independent of, and stronger than, the effects of any other hormone variable investigated. In addition, day 5 inhibin B concentrations were correlated directly with parameters of ovarian response, ovum retrieval and oocyte and fertilization outcome. However, day 5 inhibin B was not a better predictor of pregnancy than the other hormone variables studied on this day. It is concluded that inhibin B concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproductive treatment are highly predictive of ovarian response.     

Recombinant follicle stimulating hormone in in-vitro fertilization treatment-clinical experience with follitropin alpha and follitropin beta

The objective of this prospective study was to compare the outcome of ovarian hyperstimulation for in-vitro fertilization (IVF) using two different preparations of recombinant follicle stimulating hormone (FSH). The study was based on 296 consecutive IVF cycles in 1997, 199 performed using follitropin alpha (Gonal-F) and 97 performed using follitropin beta (Puregon). Outcome was compared regarding pregnancy rate, oestradiol and progesterone response, endometrial thickness, follicle number, number of retrieved oocytes, fertilized oocytes, sperm count and sperm motility. There was no significant difference in outcome of stimulation. Clinical pregnancy rate was similar, 29.1% for Gonal-F and 28.1% for Puregon. There was no difference in endometrial response, oestradiol response, number of smaller (12-15 mm) or larger (>15 mm) follicles, number of oocytes retrieved, fertilized, divided and replaced, in sperm counts or in sperm progressive motility. There was a lower follicle number in the Puregon group, but not statistically significant. The serum progesterone concentrations on the day of oocyte retrieval, however, were significantly lower in the Puregon group. In conclusion, it was not possible to find significant differences in the IVF programme with regard to stimulation outcome between Gonal-F and Puregon. The results of this study indicate that Gonal-F and Puregon may be equally suitable for use in ovarian stimulation for IVF.     

Treatment with the gonadotrophin-releasing hormone antagonist ganirelix in women undergoing ovarian stimulation with recombinant follicle stimulating hormone is effective, safe and convenient: results of a controlled, randomized, multicentre trial. The European Orgalutran Study Group

A multicentre, open-label, randomized study of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix (Orgalutran((R))/Antagon((TM))) was performed in women undergoing ovarian stimulation with recombinant FSH (rFSH: Puregon((R))). The study was designed as a non-inferiority study using a long protocol of buserelin (intranasal) and rFSH as a reference treatment. A total of 730 subjects was randomized in a treatment ratio of 2:1 (ganirelix:buserelin) using an interactive voice response system which stratified for age, type of infertility and planned fertilization procedure [IVF or intracytoplasmic sperm injection (ICSI)]. The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group, whereas the median total rFSH dose was 1500 IU and 1800 IU respectively. In addition, in the ganirelix group the mean duration of stimulation was 1 day shorter. During ganirelix treatment the incidence of LH rises (LH >/=10 IU/l) was 2.8% versus 1.3% during rFSH stimulation in the buserelin group. On the day of triggering ovulation by human chorionic gonadotrophin (HCG), the mean number of follicles >/=11 mm diameter was 10.7 and 11.8, and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively. The mean number of oocytes per retrieval was 9.1 and 10.4 respectively, whereas the mean number of good quality embryos was 3.3 and 3.5 respectively. The fertilization rate was equal in both groups (62.1%), and the same mean number of embryos (2.2) was replaced. The mean implantation rates were 15.7% and 21.8%, and the ongoing pregnancy rates per attempt were 20.3% and 25.7% in the ganirelix and buserelin groups respectively. Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated. The overall incidence of ovarian hyperstimulation syndrome was 2.4% in the ganirelix group and 5.9% in the reference group. The results of this study support a safe, short and convenient treatment regimen of ganirelix, resulting in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI.     

The development of an oocyte-containing follicle during gonadotrophin-releasing hormone agonist administration

Administration of gonadotrophin-releasing hormone (GnRH) agonist in a 29 year old woman with infertility due to ovulatory dysfunction resulted in the development of several ovarian cysts. After human chorionic gonadotrophin (HCG) was injected, the cysts were aspirated and one mature oocyte was retrieved. Intracytoplasmic sperm injection (ICSI) was performed and the resulting embryo was transferred. A singleton pregnancy was obtained and a healthy baby was born at 36 weeks of gestation. Because GnRH agonist-derived cysts may contain oocytes, we suggest that when the growth of cysts is accompanied by high concentrations of oestradiol, the administration of HCG may be useful to achieve oocyte maturation and advance IVF treatment.