The value of basal serum follicle stimulating hormone, luteinizing hormone and oestradiol concentrations following pituitary down-regulation in predicting ovarian response to stimulation with highly purified follicle stimulating hormone.

The value of gonadotrophin and oestradiol concentrations following pituitary down-regulation with leuprolide acetate in predicting ovarian response to stimulation was evaluated in three groups of women undergoing ovarian stimulation for in-vitro fertilization with highly purified follicle stimulating hormone (FSH). Leuprolide acetate was started in the midluteal phase, and either stopped at menses (IVF-SL group, n = 3), or continued throughout stimulation (IVF-LL group, n = 38; oocyte donors, n = 58). Ovarian stimulation was started on cycle day 3, after blood was drawn for down-regulated FSH, luteinizing hormone (LH) and oestradiol. Higher down-regulated LH was predictive of higher oestradiol on day 5 of stimulation in both IVF groups, and of need for fewer ampoules in the IVF-LL group, but not of oestradiol on day of human chorionic gonadotrophin (HCG) administration or number of oocytes retrieved. Higher FSH after down-regulation predicted yield of fewer oocytes in the donor and IVF-LL groups, and higher oestradiol on day 5 of stimulation, need for fewer ampoules and a shorter duration of therapy in both IVF groups. Higher oestradiol after down-regulation was associated with higher oestradiol on day 5 of stimulation and on day of HCG administration, a shorter duration of therapy and need for fewer ampoules in all groups. Whereas these results do not ascribe any predictive significance to LH, they suggest that oestradiol and FSH concentrations after down-regulation are predictive of the pattern of ovarian response to stimulation and of oocyte yield.     

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.     

Serum concentrations of follicle stimulating hormone may predict premature ovarian failure in FRAXA premutation women.

It is now recognized that female carriers of fragile X premutations are at increased risk of premature ovarian failure. We have studied 51 premenopausal women from fragile X families, to determine whether premutation carriers have variations in the hormonal markers of menopause, compared to full mutations and controls. We found a significant increase in serum follicle stimulating hormone in premutation carriers, suggesting that as a group they will enter menopause before full mutation carriers and unaffected controls. These results have important implications for fertility in these women.     

Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal serum follicle stimulating hormone levels

This study was designed to Investigate possible aetiologicalfactors involved in the low response to gonadotrophins in womenwith normal basal serum follicle stimulating hormone (FSH) concentrations,stimulated for assisted reproduction. Nine of these patientswith normal basal serum FSH and 22 normal controls (five ofwhom had had a normal response to previous gonadotrophln stimulation)were prospectively subjected to: (i) transvaginal pulsed colourDoppler ultrasound evaluation of the vessels surrounding thedominant follicle for blood flow impedance analysis, (ii) theclonidine test to explore the ability of the pituitary to releasegrowth hormone, and (iii) detection of anti-granulosa cell auto-antibodiesin blood using an enzyme-linked immunosorbent assay (ELISA).The pulsatility and resistance Indices (PI, RI) were significantly(P < 0.01) higher in the women with low responses as comparedto the controls on days –1 and 0 (day 0=ovulation). Sevenout of the nine low responders were out of the range calculatedfor normal values after evaluation of the controls. A significant(P < 0.05) decrease in the secretion of growth hormone 60–90min after clonidine ingestion was observed in the low respondersas compared to five controls with previous normal response toovarian stimulation. Six out of the nine low responders showeda negative cloiildlne test. No increase in anti-granulosa cellauto-antibodies was observed in the low responders as comparedto the controls, Including normal responders. In conclusion,an abnormal follicular blood flow impedance in the natural cyclemay be related to low responses to gonadotrophins in patientswith normal serum FSH concentrations. Simultaneously, a decreasedgrowth hormone pituitary reserve has been identified in mostof these patients, suggesting that the insulin-like growth factorssystem might be related to the vascularization of the ovarianfollicle.     

The significance of elevated basal follicle stimulating hormone in regularly menstruating infertile women

Elevated plasma follicle stimulating hormone (FSH) during thereproductive life is an early manifestation of ovarian ageing.The presence of elevated basal FSH in young, regularly menstruatingwomen may represent a stage of menopausal transition consequenton premature ovarian failure. A total of 48 regularly menstruating,infertile women aged <40 years, with high FSH and aged-matchedcontrols with normal FSH underwent detailed monitoring of endocrineand follicle growth during one complete menstrual cycle. Duringthe same cycle, detailed immunological screening was performedand the epidemiological features of all subjects were also reviewed.Subjects in the high FSH group had significantly higher basalFSH, luteinizing hormone (LH) and follicular phase LH concentrations.Despite their normal preovulatory oestradiol production, thehigh FSH group showed significantly slower follicular growth,smaller follicle diameter and lower luteal phase salivary progesterone.All these features have been described in older women duringtheir menopausal transition. In addition, the prevalence ofautoimmune antibodies was significantly higher in the high FSHgroup. This study suggests that infertile women with elevatedFSH are in their perimenopause despite having regular ovulatoryand apparently normal cycles. An autoimmune basis is suggestedas a factor underlying their premature ovarian failure. Furtherendocrinological and auto-immunological follow-up is recommended.     

Incipient ovarian failure associated with raised levels of follicle stimulating hormone and reduced levels of inhibin A in older sheep

In women there is a gradual rise in the basal level of follicle stimulating hormone (FSH) in the years prior to the menopause (pre- menopause) which is thought to be due to a relative lack of ovarian factors reflecting the number of antral follicles present in the ovaries. Experimental animal models for this phenomenon, particularly in mono-ovulatory species, have been lacking due to most animals' relatively short life span. We have available a group of experimental ewes in which the right ovary was removed and the left ovary was autotransplanted to the neck at least 10 years previously, which have been maintained in good health until an age of 12-13 years. Two experiments were conducted with these animals to determine the endocrine and follicular effects of age: a retrospective experiment in the same Finn-Merino ewes (n = 5) when the animals were 6-7 or 12-13 years of age; and a cohort experiment in old (12-13 years, n = 6) and young (2 years, n = 5) ewes of the same breed. In both retrospective and cohort experiments, the concentrations of FSH were significantly higher (P < 0.05) in older animals during the luteal phase when oestradiol secretion was low. This increase in FSH was associated with a decrease in the concentration of inhibin A (P < 0.05) in older animals in both the follicular and luteal stages of the cycle but the concentrations of oestradiol were similar between ages. Although there were significantly fewer antral follicles (P < 0.05) available for development in older ewes during the early luteal phase of the cycle, the ovulation rate was similar to that observed in younger animals (2.0+/-0 vs 2.0+/-4; P > 0.05) but the interval from luteal regression to the onset of the LH surge was longer (P < 0.05) in older animals. In conclusion, the endocrine changes associated with increasing reproductive age in sheep are therefore similar to those observed in women, suggesting that the sheep could be a useful animal model to study the effect of age on human fertility.      

A prospective, randomized, double-blind clinical trial to study the efficacy and efficiency of a fixed dose of recombinant follicle stimulating hormone (Puregon) in women undergoing ovarian stimulation

A prospective, randomized, double-blind, multicentre (n = 5) study was conducted to compare the influence of either a 100 or 200 IU daily fixed-dose regimen of recombinant follicle stimulating hormone (FSH) on the number of oocytes retrieved and the total dose used in down-regulated women undergoing ovarian stimulation. Fertilization was done by intracytoplasmic sperm injection or conventional in-vitro fertilization. A total of 199 women were treated with FSH, 101 subjects with 100 IU and 98 subjects with 200 IU. In subjects of the 200 IU treatment group, significantly more oocytes were retrieved compared to the 100 IU group (10.6 versus 6.2 oocytes, P < 0.001). The total dose needed to develop at least three follicles with a diameter of > or = 17 mm was significantly lower in the 100 IU treatment group (1114 IU versus 1931 IU, P < 0.001). In the low-dose group, significantly lower serum concentrations of oestradiol, progesterone and FSH were observed at the day of human chorionic gonadotrophin administration. Although more cycle cancellations due to low response were seen in the 100 IU group (n = 24 versus n = 3), the clinical pregnancy rate per started cycle was similar (24.7% in the 100 IU group versus 23.3% in the 200 IU group). In the high-dose group, more side-effects, in particular more cases of ovarian hyperstimulation syndrome, were noted. It is concluded that compared to 200 IU, the use of a 100 IU fixed dose is less efficacious in terms of the number of oocytes retrieved, but more efficient as indicated by a lower total dose.     

Infertility: Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles

At present, there is general agreement that ovarian stimulationimproves pregnancy rates after intra-uterine insemination (IUI).Also, ovulation induction with gonadotrophins is associatedwith higher success rates than clomiphene citrate in IUI cycles.However, the drawbacks to the use of gonadotrophin stimulationbefore IUI include the risks of ovarian hyperstimulation andmultiple gestation, and the relative cost of a treatment cyclein view of the medication costs and the need for increased monitoringby hormone assays and ultrasonographic measurements. In thepresent prospective randomized trial, the efficacy and safetyof ovarian stimulation with clomiphene citrate (50 mg/day for5 days) and IUI (clomiphene/IUI group) were compared with thoseof late low-dose pure follicle stimulating hormone (FSH, 75IU/day from day cycle 7 until the leading follicle reached >17mm in diameter) and IUI (FSH/IUI group) in ovulatory women whowere infertile because of unexplained infertility (n=40)or malesubfertility (n =60). The mean length of treatment in the FSHgroup was 6.4±2.5 days. Multiple follicular developmentwas seen in 25% of clomiphene-stimulated cycles but only in8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUIand FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively(P=0.02). All pregnancies obtained were singleton. There weretwo and one clinical abortions in the clomiphene/IUI (50%) andFSH/IUI (8%) groups respectively. No patient developed ovarianhyperstimulation syndrome. Use of our therapeutic scheme, whichproved to be efficacious, safe and economic for ovarian stimulationin IUI cycles, is advocated before the institution of in-vitrofertilization (IVF) or gamete intra-Fallopian transfer (GIFT)therapy in infertile patients with patent Fallopian tubes. Thislate low-dose technique of administering pure FSH is suitablefor use in offices without immediate access to oestradiol results.     

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.     

Pregnancies after oocyte donation in women with ovarian failure caused by an inactivating mutation in the follicle stimulating hormone receptor.

BACKGROUND: An inactivating point mutation (Ala189Val) in the FSH receptor (FSHR) causes primary ovarian failure. It has not been known if FSH action is necessary during pregnancy and childbirth. METHODS: In 1991-2001, donated oocytes were used to treat the infertility of 12 women with ovarian failure due to this mutation. RESULTS: When 30 fresh and 15 frozen-thawed embryo transfers were performed, 14 clinical and two biochemical pregnancies resulted. To date, 12 children have been born to eight women, while one pregnancy ended in miscarriage. Three women had twin pregnancies, and one woman has delivered twice. Additionally, there are three ongoing pregnancies, of which two are second pregnancies of women who previously had a normal delivery after similar treatment. In all, 10 out of the 12 women became pregnant. Two deliveries were by Caesarean section. The rate of complications was comparable with that in pregnancies resulting from oocyte donation in general. CONCLUSIONS: Achieving and undergoing a successful pregnancy is possible when FSH action is severely decreased. Oocyte donation is an effective infertility treatment for women with FSHR mutations.     

A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon((R))) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP((R))) in a fixed-dose regimen in women undergoing ovarian stimulation.

A prospective, randomized, open, multicentre (n = 3) study was conducted to compare the efficacy and efficiency of a fixed daily dose of 150 IU (3x50 IU) recombinant follicle stimulating hormone (recFSH, Puregon((R))) and 225 IU (3x75 IU) highly purified urinary FSH (uFSH-HP, Metrodin-HP((R))) in women undergoing ovarian stimulation prior to in-vitro fertilization treatment. A total of 165 women were treated with FSH, 83 subjects with recFSH and 82 subjects with uFSH-HP. In the recFSH group a mean number of 8.8 oocytes were retrieved, compared with 9.8 in the uFSH-HP group (not statistically significant). In the recFSH group, a significantly lower total dose was required compared to the uFSH-HP group, 1479 versus 2139 IU, respectively (P < 0.0001; 95% confidence interval -747 to -572). Treatment with recFSH resulted in a significantly higher embryo development rate (69.6 versus 56.2%; P = 0.003) and more embryos accessible for the embryo freezing programme (3.3 versus 2.0; P = 0.02) compared to uFSH-HP. The vital pregnancy rate per cycle started was 30.2 versus 28.3% in the recombinant and urinary FSH group, respectively. It is concluded that treatment outcome of a fixed daily dose of 150 IU recFSH is comparable to a fixed daily dose of 225 IU uFSH-HP. However, a significantly lower total dose was needed in the recFSH group (nearly 700 IU less).     

Octreotide, a somatostatin analogue, alters ovarian sensitivity to gonadotrophin stimulation as measured by the follicle stimulating hormone threshold in polycystic ovary syndrome

The aim of the present study was to determine the effect of octreotide, a somatostatin analogue, on ovarian sensitivity for follicle stimulating hormone (FSH) in patients with polycystic ovary syndrome (PCOS). As the measure of ovarian sensitivity, the FSH threshold was determined in a case-control set-up. Eleven patients with PCOS were treated with FSH in a low dose step-up manner and subsequently received treatment with FSH combined with octreotide. The FSH threshold was found to be significantly higher during combined treatment. This increase was associated with a decrease in insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) concentrations during treatment with octreotide, but not with a decrease in insulin concentrations. No differences were found between the two regimens, in number of follicles, in oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration or in ovulation rate. With both treatments, there was a very low rate of multifollicular development. It can be concluded that octreotide lowers ovarian sensitivity for FSH through suppression of IGF-I/IGFBP-3 in patients with PCOS. However, this does not appear to affect follicular development during gonadotrophin stimulation, because the latter is controlled to a high degree by the use of a low dose step-up treatment schedule in these patients.      

Effect of follicle stimulating hormone treatment on the pituitary response to luteinizing hormone-releasing hormone in post-menopausal women

To study the role of exogenous follicle stimulating hormone(FSH) in the attenuation of luteinizing hormone (LH) responseto luteinizing hormone-releasing hormone (LHRH) during ovulationinduction in women, 10 healthy post-menopausal women were treatedwith FSH (225 IU/day) for 5 days and normal saline (2 ml/day)for another 5 days. The two regimens were given consecutivelyin a 10 day experiment. The regimen for the first 5 days wasrandomly chosen and was given to the women in an alternate way.The response of LH to an i.v. injection of 10 µg LHRHwas investigated twice on day 1 (i.e. before the onset of treatmentand 12 h later) and once on days 2, 5 and 10 of the experiment(0900 h). Basal FSH and LH values before the onset of treatmenton day 1 were similar in the five women who started with thesaline and the five who started with the FSH regimen. BasalFSH values increased significantly during treatment with FSH,while LH and oestradiol values remained unchanged throught thewhole experiment. LH increment 30 min post –LHRH did notchange significantly either during the first 24 h or duringthe whole experiment regardless of the starting regimen. Theseresults demonstrate that in post-menopausal women the responseof LH to LHRH is not affected by exogenous administration ofFSH. It is suggested that exogenous FSH does not show activitieson gonadotrophin secretion similar to those ascribed to a gonadotrophinsecretion similar to those ascribed to a gonadotrophin surgeattenuating factor.     

Increased risk of early pregnancy loss by profound suppression of luteinizing hormone during ovarian stimulation in normogonadotrophic women undergoing assisted reproduction

The impact of suppressed concentrations of circulating luteinizing hormone (LH) during ovarian stimulation on the outcome of in-vitro fertilization or intracytoplasmic sperm injection treatment in 200 consecutive, normogonadotrophic women (couples) was analysed retrospectively. A standard stimulation protocol with mid-luteal gonadotrophin-releasing hormone (GnRH) agonist down-regulation and ovarian stimulation with recombinant follicle stimulating hormone (FSH) was used in all cases. Blood was sampled from each woman on stimulation days 1 and 8 for analysis of oestradiol and LH in serum. A threshold value of serum LH of 0.5 IU/l on stimulation day 8 (S8) was chosen to discriminate between women with low or 'normal' LH concentrations. Low concentrations of LH on S8 (<0.5 IU/l) were found in 49% (98/200) of the women. This group of women was comparable with the normal LH group with regard to pre-treatment clinical parameters, and to the parameters characterizing the stimulation protocol with the exception of serum oestradiol concentration, which on S8 was significantly lower than in the normal LH group (P < 0.001). The proportion of positive pregnancy tests was similar in the two groups (30% versus 34% per started cycle), but the final clinical treatment outcome was significantly different, with a five-fold higher risk of early pregnancy loss (45% versus 9%; P < 0.005) in the low LH group and consequently a significantly poorer chance of delivery than in the normal LH group. It is concluded that a substantial proportion of normogonadotrophic women treated with GnRH agonist down-regulation in combination with FSH, devoid of LH activity, experience LH suppression, which compromises the treatment outcome. Whether these women would benefit from supplementation with recombinant LH or human menopausal gonadotrophin during ovarian stimulation, remains to be proven in the future by prospective randomized trials.     

Effects of profound suppression of luteinizing hormone during ovarian stimulation on follicular activity, oocyte and embryo function in cycles stimulated with purified follicle stimulating hormone

The effects of profound suppression of circulating luteinizing hormone (LH) during the follicular phase of in-vitro fertilization cycles were explored in normal women during treatment with a gonadotrophin- releasing hormone analogue and exogenous purified follicle stimulating hormone. Ovarian responses to treatment and the capacity of supernumerary embryos to undergo blastocyst formation were examined in groups of patients defined by the concentration of plasma LH in the mid- follicular phase. Concentrations < or = 0.5 IU/I diagnosed the group with profoundly suppressed LH (<LH, n = 20), which was compared with the remaining patients (nLH, n = 41). The <LH group showed lower oestradiol concentrations at human chorionic gonadotrophin administration, while the total follicular development estimated by the total follicular diameters was similar in both groups. The oestradiol secreted per follicle, estimated by the circulating concentration per mm total follicular diameter, was significantly lower in the <LH group. The combined effects of a trend to lower yield of oocytes (not significant) and a lower fertilization rate (not significant) resulted in a significantly reduced quantity of embryos available for cryopreservation after the fresh transfer. Supernumerary embryos were cultured for 7 days to determine blastocyst development rates, and the degree of LH suppression made no difference to embryo developmental competence (nLH, 23%; <LH, 27%), or the rates of blastocyst formation. The group of patients with profoundly suppressed mid-follicular phase LH showed a reduced yield of oocytes and embryos which resulted in significantly fewer embryos available for cryopreservation. However, the developmental potential of those embryos, represented by the ability to form blastocysts in vitro, was unaffected.      

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.     

卵泡刺激素受体基因多态性与西北地区汉族妇女卵巢反应性的关系

目的探讨卵泡刺激素受体基因（FSHR）-29（rsl394205）和Asn680Ser（rs6166）位点多态性与西北地区汉族妇女控制性超排卵（COH）中卵巢反应性的关系。方法采用限制性酶切技术对卵巢高反应患者45例,卵巢低反应患者27例和卵巢正常反应的对照69例的FSHR基因-29（rsl394205）位点和第10号外显子Asn680Ser（rs6166）位点进行分型,并通过Fisher’s精确检验的方法分析基因型和等位基因的分布频率。结果①FSHR基因-29位点基因型、等位基因频率在三组间分布无差异。②Asn680Ser位点基因型、等位基因频率在卵巢高反应组与正常对照组间无统计学差异（P〉0．05）;Ser／Ser基因型频率在卵巢低反应中占40．7％,与正常对照组差异有统计学意义（P〈0．01）;携带G等位基因者发生卵巢低反应的风险增加（OR=2．37,％95CI=[1．25-4．52]）。结论FSHRAsn680Ser位基因多态性与西北地区汉族妇女COH中的卵巢低反应相关。当Asn680Ser（rs6166）位点G等位基因的存在增加卵巢低反应的风险。     

Effect of antagonists of dopamine and opiates on the basal and GnRH-induced secretion of luteinizing hormone, follicle stimulating hormone and prolactin during lactational amenorrhoea in breastfeeding women

The role of dopamine and opiates in the suckling-induced suppressionof gonadotrophin secretion and prolactin release was investigatedduring lactational amenorrhoea in fully breastfeeding womenat 12 weeks post-partum. A total of 26 women, 20 using non-steroidalmethods of contraception and six using the progestogen-onlypill, Noriday (POP), breastfed their babies on demand at a frequencyof 3.6 ± 0.2 suckling episodes during the 8 h study periodwhile blood samples were collected at 10-min intervals. Fivehours after the start of sampling six women were given the dopamineantagonist metoclopramide (10 mg, i.m.) while four women receivedsaline. In a second experiment, six women using nonsteroidalcontraception and three women on the POP received an i.v. infusionof the opiate antagonist naloxone (1.6 mg/h) for 2 h, whilefour women using non-steroidal contraception and three womenon the POP were infused with saline. Two hours after the i.m.injection or start of infusion all women were given an i.v.injection of 10 µg gonadotrophin releasing hormone (GnRH)and samples were collected for a further 1 h. All samples wereassayed for luteinizing hormone (LH), follicle stimulating hormone(FSH) and prolactin. Plasma concentrations of oestradiol were<60 pmol/l in all women and they remained amenorrhoeic forat least 10 weeks after the study. Pulsatile release of LH wasonly observed over the 5 h pre-treatment period in 10 of the20 non-steroid taking women (1–3 pulses/5 h), and in oneof the six women (1 pulse/5 h) on POP. Treatment with metoclopramidecaused a substantial (29-fold) increase in prolactin over baseline,7.4 times the maximum released in response to suckling. Therewas no effect of metoclopramide on the pattern of release ofLH or FSH or the response to GnRH. Infusion of naloxone in womenusing either non-steroidal contraceptives or progestogen-onlypill did not affect prolactin release. Naloxone infusion didnot affect LH or FSH in women using nonsteroidal contraceptives,but caused a small but significant (P < 0.05) increase inboth LH and FSH in women taking the progestogen-only pill. Therewas a significantly greater release of LH and FSH after GnRHin all women after naloxone infusion. These results in breastfeedingwomen during lactational amenorrhoea confirmed that sucklingsuppresses the pulsatile release of LH but not through a dopaminergicpathway, showed that prolactin remains under dopaminergic controlduring human lactation, but suckling does not appear to affectprolactin secretion via an opiate pathway and indicated onlya minor, if any, role for opiates in the sucklinginduced suppressionof GnRH/gonadotrophin secretion but a potential, previouslyunreported, effect of opiates in reducing pituitary responsivenessto GnRH.     

Andrology: Effect of growth hormone administration on circulating levels of luteinizing hormone, follicle stimulating hormone and testosterone in normal healthy men

A new area of growth hormone (GH) therapy in adults is the treatmentof infertility. The aim of this study was to evaluate the effectsof pharmacological GH administration on the secretion of pituitaryand gonadal hormones in normal men. Eight healthy men, 23–32years of age (mean 28.1 years), with a normal body mass indexwere studied in a double-blind, placebo-controlled crossoverdesign. All participants had a normal semen analysis beforeentering the study. Each participant was treated with placeboand GH (12/IU/day, Norditropin; Novo Nordisk, Denmark) duringtwo different 14-day periods, separated by a 6 week washoutperiod. Administration of GH for 14 days resulted in a significantincrease in serum insulin-like growth factor I (IGF-I; P <0.01) but no changes occurred in IGF-I values during placebotreatment. The concentrations of follicle stimulating hormoneand luteinizing hormone displayed no change during the two periodsand did not differ between the GH treatment period and the placeboperiod. The concentration of testosterone was unchanged duringthe placebo/GH periods and there was no difference between theGH treatment period and the placebo period. We conclude thatGH treatment for 14 days in normal healthy men does not affectgonadotrophin or testosterone patterns.     

Discrimination between chronological and ovarian age in infertile women aged 35 years and older: predicting pregnancy using basal follicle stimulating hormone, age and number of ovulation induction/intra-uterine insemination cycles

A marked decline in fertility rates has been demonstrated inwomen >35 years of age. We have previously demonstrated theimportance of basal follicle stimulating hormone (FSH) concentrationsplus chronological age to predict pregnancies in women aged40 years undergoing ovula-tion induction therapy. The purposeof the current study was to extend our previous study and determinethe impact of age, basal FSH concentrations and ovulation induction/intra-uterine insemination (IUI) treatment cycles on pregnancyrates in infertile women aged 35 years. This prospective observationalstudy was performed at a tertiary university fertility centre.Assessments of basal hormonal status and ovulation inductionprotocols were performed. The main outcome measured was clinicalpregnancies. A total of 770 treatment cycles in 179 women aged35 years were analysed. The impact of basal FSH concentrationson treatment outcomes could be bifurcated into a favourablegroup (FSH 23 mlU/ml) and a poor prognosis group (FSH 24 mlU/ml).A multivariate logistic regression model was generated whichaccurately predicted pregnancies. There was a high degree ofcorrelation between predicted pregnancies and observed pregnancies(r = 0.86). We conclude that age, number of treatment cyclesand the interaction term basal FSH x age are useful and significantpredictors of pregnancies in patients aged 35 years undergoingovulation induction/IUl therapy.