Serum IGF-1 concentrations following pituitary desensitization do not predict the ovarian response to gonadotrophin stimulation prior to IVF

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is known to play a role in ovarian follicular development augmenting the action of FSH. Low intrafollicular concentrations have been detected in women who respond poorly to gonadotrophins. This study addresses the relationship between serum IGF-1 levels following pituitary desensitization and ovarian response to gonadotrophin stimulation. METHODS: This is a case-control study of 78 patients undergoing IVF-embryo transfer treatment. Thirty-nine strictly-defined poor responder patients requiring 50 or more ampoules (75 IU FSH) to reach oocyte retrieval were compared with 39 age-matched normal responders, requiring fewer than 50 ampoules. IGF-1 concentrations were determined by extraction radioimmunoassay on serum samples obtained after pituitary desensitization but prior to gonadotrophin stimulation. RESULTS: Despite highly significant differences in measures of ovarian response between groups, the mean serum IGF-1 concentration was not statistically significantly different between poor and normal responders [(31.5 nmol/l [95% confidence interval (CI) 28.5-34.5] versus 34.5 nmol/l (95% CI 31.8-37.2)] respectively. No correlation between oocyte number or total gonadotrophin used and serum IGF-1 concentration was observed. CONCLUSION: Whilst IGF-1 influences ovarian follicular development this study suggests that serum IGF-1 does not predict ovarian response and does not differentiate between critically-defined poor and normal responders.     

Immunity to zona pellucida in women with low response to ovarian stimulation, in unexplained infertility and after multiple IVF attempts

A retrospective study was designed to assess the presence ofantizona pellucida autoantibodies in in-vitro fertilization(IVF) patients in relation to low ovarian response, multipleIVF attempts and unexplained infertility. Antizona pellucidaand antisperm antibodies were determined in serum samples obtainedfrom 37 women undergoing IVF-embryo transfer and 20 fertilewomen. Antizona pellucida antibodies were measured using enzymeimmunoabsorbent assay. Antisperm antibodies were evaluated bythe immunobead binding method. Three of 10 patients with lowresponse to ovarian stimulation had antizona pellucida antibodiesin serum and one patient had antisperm antibodies. None of theother participants in the study and the control groups demonstratedmeasurable levels of serum antigamete antibodies. The resultsin this small group suggest an association between antizonapellucidaantibodies and suboptimal response to gonadotrophins. It isindicated that repeated stimulation and puncture of ovariesin IVF procedures do not elicit auto-immunity to gametes.     

Predictors of low response to mild ovarian stimulation initiated on cycle day 5 for IVF

BACKGROUND: Milder stimulation protocols are being developed to minimize adverse effects of ovarian stimulation in in vitro fertilization (IVF) programs. A drawback is the possibility of an increased rate of insufficient ovarian response. This study aimed to develop a prognostic model for the prediction of cycle cancellation due to insufficient response to mild stimulation. METHODS: A total of 174 IVF patients aged<38 years and with a body mass index (BMI)<28 Kg/m2 were treated with mild ovarian stimulation using a fixed daily dose (150 IU) of recombinant follicle-stimulating hormone (rFSH) from cycle day 5 and GnRH antagonist from the late follicular phase. In women with mono- or bifollicular growth (17%), the cycle was cancelled and the treatment was adjusted in a second treatment cycle by starting rFSH on cycle day 2. RESULTS: In a multivariable logistic regression analysis, duration of infertility, menstrual cycle length, secondary infertility and BMI were included in the prediction model. The area under the receiver-operating characteristics curve of the model was 0.69. A probability cut-off for cancellation of 0.3 yielded an expected sensitivity of 33% and specificity of 92%. Analysis of ovarian response in the subsequent treatment cycle showed an improved ovarian response and a significant reduction in the cancellation rate. CONCLUSIONS: With the presented model, it is possible to identify patients at risk for cycle cancellation, during mild ovarian stimulation, due to insufficient response. The contributing factors of the model suggest that ovarian aging and BMI are related to insufficient response to mild stimulation.     

Establishing pregnancies after follicular stimulation for IVF with clomiphene citrate and human menopausal gonadotrophin only

Data are presented on establishing pregnancies by IVF during 1987 using only clomiphene citrate and human menopausal gonadotrophin for follicular stimulation. Of the 562 patients undergoing follicular stimulation, 80% reached oocyte recovery and 70% had at least one conceptus replaced. Patients having one or more (up to a maximum of four) conceptuses replaced demonstrated a significant increase in the establishment of pregnancies from one to two (14-29%: P = 0.035) and from two to three conceptuses (29-42%: P = 0.037). There was a significant decline in pregnancies when four conceptuses were replaced compared with three (P = 0.004). The data were also analysed according to the cause of infertility, specifically tubal, endometriosis, unexplained infertility and male factors only. After the replacement of conceptuses, the incidence of implantation and abortion was not significantly different. The incidence of pregnancy declined significantly after 35 years (26%) compared with women under 31 years (43%; P = 0.043). Of 129 women having three conceptuses replaced, in those greater than 35 years (63 patients) 23 (37%) became pregnant whereas in those less than 31 years (65 patients), 34 (52%; P = 0.05) became pregnant. Twenty-two per cent of stimulated cycles resulted in an endogenous LH surge and the incidence of patients having three conceptuses replaced in this group was lower than those in the HCG group (P = 0.007). Fertilization per oocyte was also significantly reduced (P less than 0.001) in patients with an LH surge. In total, 2824 oocytes were recovered and 57% fertilized with 54% of patients having three conceptuses replaced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular endothelial growth factor levels in serum and plasma from patients undergoing controlled ovarian hyperstimulation for IVF

BACKGROUND: Vascular endothelial growth factor (VEGF) has been investigated as a marker of ovarian response to controlled ovarian hyperstimulation and as a predictor of ovarian hyperstimulation syndrome (OHSS) in IVF cycles. In most studies, serum has been used for circulating VEGF concentration measurement, but it has been suggested that plasma is the preferred medium to measure VEGF levels because of the potential contribution of VEGF released from platelets during blood clotting. This study investigated VEGF concentrations in paired serum and plasma samples from patients undergoing controlled ovarian hyperstimulation for IVF. METHODS: Serum and plasma VEGF levels, as well as the number of platelets, were measured in 30 IVF patients who comprised three study groups delineated according to the estradiol (E(2)) serum concentration reached on the day of HCG administration: 10 patients having low E(2) serum levels (<1500 pg/ml, group L), 10 patients having intermediate E(2) serum levels (1500-3000 pg/ml, group I) and 10 patients having high E(2) serum levels (>3000 pg/ml, group H). RESULTS: There was a statistically significant correlation between plasma and serum VEGF levels (rho = 0.61; P < 0.005) for the entire population studied, although serum values were higher by a factor of approximately 6-fold. No significant correlation was found between peripheral blood VEGF concentrations and serum E(2) or follicle number on HCG day or the number of oocytes collected. Similarly, paired serum and plasma VEGF measurements did not correlate with platelet count. CONCLUSIONS: Serum and plasma VEGF concentrations are strongly correlated in paired samples from infertile patients undergoing controlled ovarian hyperstimulation. However, neither serum nor plasma VEGF levels were correlated with parameters associated with ovarian follicular activity. Peripheral blood VEGF levels were not correlated with platelet count.     

Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation

BACKGROUND: The effect of LH levels on stimulation day 8 on ovarian response and pregnancy outcome were evaluated in women receiving pituitary down-regulation with GnRH agonists (0.8 mg Suprefact) s.c. daily until pituitary down-regulation and 0.4 mg/day during ovarian stimulation) and ovarian stimulation with recombinant FSH. METHODS: Blood samples were prospectively collected from a total of 207 normal women undergoing assisted reproduction and analysed retrospectively. Based on LH levels on stimulation day 8 patients were divided into four groups: <0.5, 0.51-1.0, 1.01-1.5, >1.51 IU/l. RESULTS: Estradiol levels on day 8 and estradiol per oocyte retrieved showed a highly significant correlation with LH concentrations on day 8. The total consumption of exogenous FSH and duration of gonadotrophin stimulation was inversely related to LH levels on day 8 (P < 0.002). The frequencies of fertilization and clinical pregnancies were superior in the two middle groups. Only 12% of the patients showed LH levels <0.5 IU/l, which, however, may be explained by the particular mode and doses of GnRH agonist used. CONCLUSIONS: Circulating levels of LH on day 8 have a significant impact on ovarian response and pregnancy outcome. LH should neither be too high nor too low. The mode of administration and the dose of the GnRH agonist used may determine the number of women who experience LH levels below 0.5 IU/l.     

CTG amplification in the DM1PK gene is not associated with idiopathic male subfertility

BACKGROUND: Polymorphism in the CTG triplet number in the myotonic dystrophy type 1 (DM1PK) gene has been proposed as being associated with idiopathic azoospermia. The aim of this study was to investigate whether the CTG trinucleotide amplification in the DM1PK gene is associated with male subfertility. METHODS: We evaluated 107 subfertile patients, male partners of infertile couples, affected by non-obstructive azoospermia (n = 38) and oligoasthenoteratozoospermia (OAT) (n = 69), and 102 men with proven fertility. Main outcome measures were CTG repeat size in the DM1PK gene, testicular volume, sperm concentration, rapid progressive motility, normal morphology, serum FSH levels, testicular histology and Johnsen score. RESULTS: In subfertile males, no minimal mutation or mutation carriers were found. The difference in the number of CTG repeat lengths between the groups was not statistically significant (P = 0.825). There was no correlation between the number of CTG repeats and the clinical parameters of subfertile patients: testicular volume, sperm concentration, rapid progressive motility, normal morphology, FSH level, testicular histology and Johnsen score. CONCLUSIONS: The number of CTG repeats in the normal or mutational range of DM1PK gene is associated with neither idiopathic male subfertility nor with clinical characteristics of male subfertility.     

Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.     

Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome

BACKGROUND: Poor ovarian response limits IVF success but assessing interventions is difficult because of the wide variation in definition. This study attempts to derive objective definitions of poor response. METHODS: A retrospective study of a consecutive series of 1190 patients aged <40 years undergoing their first IVF/ICSI cycle was undertaken. Factors adversely affecting implantation, including advanced female age, were excluded. Clinical outcome in cycles reaching oocyte retrieval (n = 1036) were evaluated with respect to gonadotrophin dose used and oocyte number. Cancelled cycles (n = 154) were analysed in relation to the stimulation dose at cancellation and outcome of their subsequent cycle. RESULTS: Cycle cancellation for patients on >/=300 IU FSH/day compared to those on a lower dose was associated with a significantly worse outcome in the subsequent cycle. If <3000 IU FSH/cycle were administered, clinical pregnancy rates remained favourable if <4 eggs were recovered (29 versus 33% for >/=5 eggs). By contrast, if >/=3000 IU FSH was required, the pregnancy rate was 25% if >/=5 eggs were recovered but declined to 7% if <4 were obtained. CONCLUSIONS: Definitions of poor response should include the degree of ovarian stimulation used. A low oocyte number is only detrimental if the cumulative dose is >3000 IU FSH. Cancellation at >/=300 IU FSH/day is associated with a significantly worse prognosis and could define poor response.     

Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme

BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonadotrophins is a significant problem in assisted reproduction. Various adjuvant treatments have been suggested to improve responsiveness. This study reports on the potential benefits of low dose dexamethasone. METHODS: Patients <40 years of age were invited to participate in a twin centre prospective double blind randomized placebo controlled study. A total of 290 patients were recruited and computer randomized using sealed envelopes to receive either 1 mg dexamethasone (n = 145) or placebo tablets (n = 145) in addition to a standard long protocol gonadotrophin-releasing hormone analogue with gonadotrophin stimulation regime. RESULTS: A significantly lower cancellation rate for poor ovarian response was observed in the dexamethasone group compared with controls (2.8 versus 12.4% respectively, P < 0.002). Further comparisons between the dexamethasone group and controls were made of median fertilization rates (60 versus 61% respectively, NS), implantation rates (16.3 versus 11.6% respectively, NS) and pregnancy rate per cycle started (26.9 versus 17.2%, NS). The benefit was apparent in patients both with polycystic and normal ovaries. CONCLUSION: Low dose dexamethasone co-treatment reduces the incidence of poor ovarian response. It may increase clinical pregnancy rates and should be considered for inclusion in stimulation regimes to optimize ovarian response.     

Percentile curves of serum estradiol levels during controlled ovarian stimulation in 905 cycles stimulated with recombinant FSH show that high estradiol is not detrimental to IVF outcome

BACKGROUND: High, normal and poor responders are usually defined by reference to subjectively selected estradiol E2 levels at days 4-6 and the day of hCG administration (d-hCG). The purpose of this study was to use E2 percentile curves from day 5 until d-hCG to determine high, normal and poor responders, and to predict IVF outcome. METHODS: In this retrospective study, 762 patients underwent 905 cycles with a GnRH agonist/recombinant FSH short protocol. They were divided into three groups according to their age. Percentile E2 curves according to E2 levels were plotted. High responders were those patients with E2 levels above the 90th percentile, normal responders had E2 between the 10th and 90th percentiles, and poor responders had E2 below the 10th percentile. RESULTS: IVF outcome, expressed as number of oocytes, total embryos obtained and number of high grade embryos, was significantly better for patients with E2 above the 90th percentile at d-hCG for the three age groups and at day 5 for group A (<35 years). Pregnancy rates were higher for high responders, but the difference did not reach statistical significance. CONCLUSIONS: Percentile curves can be useful in controlled ovarian stimulation cycles to define high, normal and poor responders, and also to predict IVF outcome.     

An open,randomized single-centre study to compare the efficacy and convenience of follitropin beta administered by a pen device with follitropin alpha administered by a conventional syringe in women undergoing ovarian stimulation for IVF/ICSI

BACKGROUND: A pen device, similar to an insulin pen, has been recently marketed for the administration of follitropin beta in cartridges. A randomized controlled trial was performed to compare the efficacy and convenience of this pen device delivering follitropin beta with a conventional syringe delivering follitropin alpha. METHODS: A total of 200 patients needing IVF/ICSI treatment and willing to self-inject were enrolled in the study. All subjects had ovarian stimulation according to a long protocol and were randomized to the pen or the conventional syringe group during down-regulation by means of a computer-generated randomization list using random numbers. Patients were asked to fill in a daily local tolerance book after each injection. On the day of hCG the patients scored a Visual Analogue Scale (VAS) for pain and convenience. RESULTS: The average duration, total dose of recombinant FSH and number of cumulus oocyte complexes retrieved were 10.8/12.0 days (P = 0.001), 1880/2226 IU (P < 0.001) and 15.2/13.1 respectively in the pen device and conventional syringe groups; the presence of pain after the daily injection was significantly higher in the conventional syringe group (P = 0.027); the visual analogue scale score was similar for pain but significantly more convenient for the pen device (P < 0.001). The live birth rate per embryo transfer was 32.9 and 34.4% respectively in the pen device and conventional syringe groups. CONCLUSIONS: Self-injection with the pen device is safe and easy, more convenient and less painful for the patient, requires less FSH and shortens the treatment duration.     

Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility

BACKGROUND: Adding clomiphene citrate (CC) to FSH for controlled ovarian stimulation (COS) decreases FSH dose required for optimum stimulation. However, because of its anti-estrogenic effects, CC may be associated with lower pregnancy rates offsetting the FSH-dose reduction benefit. Previously, we reported the success of aromatase inhibition in inducing ovulation without antiestrogenic effects. METHODS: A prospective pilot study that included women with unexplained infertility undergoing COS and intrauterine insemination. Thirty-six women received the aromatase inhibitor letrozole + FSH, 18 women received CC + FSH and 56 women received FSH only. Each woman received one treatment regimen in one treatment cycle. All patients were given recombinant or highly purified FSH (50-150 IU/day) starting on day 3 to 7 until day of hCG. RESULTS: The FSH dose needed was significantly lower in letrozole + FSH and CC + FSH groups compared with FSH-only without a difference in number of follicles >1.8 cm. Pregnancy rate was 19.1% in the letrozole + FSH group, 10.5% in the CC + FSH group and 18.7% in the FSH-only group. Both pregnancy rate and endometrial thickness were significantly lower in CC + FSH group compared with the other two groups. Estradiol (E2) levels were significantly lower in the letrozole + FSH group compared with the other two groups. CONCLUSIONS: Similar to CC, aromatase inhibition with letrozole reduces FSH dose required for COS without the undesirable antiestrogenic effects sometimes seen with CC.     

Follicular fluid concentrations of adrenomedullin, vascular endothelial growth factor and nitric oxide in IVF cycles: relationship to ovarian response

Marked granulosa cell proliferation along with important changes in the vascular bed of the ovary characterize IVF cycles associated with multiple follicular growth and maturation. The present report investigated follicular fluid (FF) and circulating concentrations of adrenomedullin, vascular endothelial growth factor (VEGF) and nitric oxide (NO) in 70 IVF patients (14 of whom became pregnant); these three vasoactive substances may be implicated in extensive ovarian tissue remodelling. Serum and FF concentrations of oestradiol and progesterone were also measured in the 70 IVF cycles studied. Follicular fluid concentrations of VEGF and adrenomedullin but not nitrite/nitrate (the two stable oxidation products of NO metabolism) were significantly higher (P < 0.0001) than the corresponding circulating concentrations. Follicular fluid concentrations of oestradiol and progesterone were not correlated with those of adrenomedullin, VEGF or nitrite/nitrate. No relationship existed between circulating concentrations of adrenomedullin, VEGF or nitrite/nitrate on the day of oocyte aspiration and parameters of ovarian response to gonadotrophin stimulation. In contrast, FF adrenomedullin concentration showed a direct relationship with day 3 FSH serum concentration (r = 0.53, P < 0.01) and the number of ampoules of gonadotrophin administered (r = 0.36, P < 0.005), but an inverse correlation with the total number of oocytes retrieved (r = -0.29, P < 0.01) and the number of mature oocytes (r = -0.25, P < 0. 05). A positive correlation was found for FF VEGF concentration and chronological age (r = 0.29, P < 0.05) and ampoules of gonadotrophins administered (r = 0.30, P < 0.05). There was no relationship between nitrite/nitrate FF concentrations and parameters of ovarian response. Neither serum concentrations nor FF concentrations of adrenomedullin, VEGF or nitrite/nitrate were correlated with IVF outcome. This study suggested for the first time that increased FF concentrations of adrenomedullin can be a marker of decreased ovarian response in IVF. Our results also provide further evidence favouring an association between FF VEGF and patient's age, while on the basis of our findings NO measurements are not a useful marker of ovarian response.     

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.     

Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis

BACKGROUND: The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. METHODS: We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10), group B patients with 5-14 follicles (n = 10) and group C patients with >15 follicles (n = 10). RESULTS: Mean (+/-SD) VEGF concentrations in follicular fluid were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5, 23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). CONCLUSIONS: Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.     

Basal and stimulation day 5 anti-Mullerian hormone serum concentrations as predictors of ovarian response and pregnancy in assisted reproductive technology cycles stimulated with gonadotropin-releasing hormone agonist--gonadotropin treatment

BACKGROUND: Anti-Müllerian hormone (AMH) has been recently proposed as a marker for ovarian ageing and poor ovarian response to controlled ovarian hyperstimulation in assisted reproduction cycles. The present study was undertaken to investigate the usefulness of baseline cycle day 3 AMH levels and AMH serum concentrations obtained on the fifth day of gonadotropin therapy in predicting ovarian response and pregnancy in women undergoing ovarian stimulation with FSH under pituitary desensitization for assisted reproduction. METHODS: A total of 80 women undergoing their first cycle of 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 reproduction programme matching by race, age, body mass index, basal FSH and indication for IVF/ICSI to those in the cancelled group. For each cancelled patient, three IVF/ICSI women who met the matching criteria were included. RESULTS: Basal and day 5 AMH serum concentrations were significantly lower in the cancelled than in the control group. Receiver-operating characteristic (ROC) analysis showed that the capacity of day 5 AMH in predicting the likelihood of cancellation in an assisted reproduction treatment programme was significantly higher than that for basal AMH measurement. However, the predictive capacity of day 5 AMH was not better than that provided by day 5 estradiol. In addition, neither basal nor day 5 AMH or estradiol measurements were useful in the prediction of pregnancy after assisted reproductive treatment. CONCLUSIONS: AMH concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproduction are better predictors of ovarian response than basal AMH measurements. However, AMH is not useful in the prediction of pregnancy. Definite clinical applicability of AMH determination as a marker of IVF outcome remains to be established.     

A prospective, randomized comparison of two starting doses of recombinant FSH in combination with cetrorelix in women undergoing ovarian stimulation for IVF/ICSI

BACKGROUND: A prospective randomized study was carried out in two centres to compare the number of oocytes retrieved after two different starting doses of recombinant human FSH (rhFSH) (Gonal-F) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) cycles using the multiple dose regimen of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix (Cetrotide) to prevent induction of the premature LH surge. METHODS: Sixty women were randomized to receive rhFSH 150 IU ('low'), and 60 women to receive rhFSH 225 IU ('high') as the starting dose for the first 5 days of stimulation. From stimulation day 6 and onwards, including the day of human chorionic gonadotrophin (HCG) administration, the women received 0.25 mg of cetrorelix as a daily dose. The primary endpoint was the number of oocytes retrieved. RESULTS: The mean number (+/- SD) of oocytes was 9.1 +/- 4.4 and 11.0 +/- 4.6 in the 'low' and 'high' groups respectively (P = 0.024). The mean number of 75 IU ampoules of rhFSH was significantly lower in the 'low' group (23.0 +/- 6.3 versus 30.5 +/- 5.6, P < 0.0001). The ongoing pregnancy rate per started cycle and per embryo transfer were 25.9 and 28.8% versus 25.4 and 26.8% respectively in the 'low' and 'high' rhFSH groups (P = NS). CONCLUSIONS: When using a starting dose of 225 IU rhFSH combined with the multiple dose of 0.25 mg cetrorelix from stimulation day 6, significantly more oocytes were obtained than with a starting dose of 150 IU rhFSH.     

The influence of body mass index, basal FSH and age on the response to gonadotrophin stimulation in non-polycystic ovarian syndrome patients

BACKGROUND: Adequate ovarian response to exogenous gonadotrophins is important for both ovulation induction (OI) and controlled ovarian stimulation (COS). The objective of this study was to analyse the effect of a number of clinical factors that influence ovarian response in non-polycystic ovarian syndrome (non-PCOS) patients. METHODS: A total of 140 OI cycles (52 subjects), where each subject had a single abnormality (elevated FSH, abnormal body mass index (BMI) or > or = 40 years of age), were compared with 54 cycles (15 subjects) where the patients displayed none of these abnormal features (the normal group). Similarly, 275 COS cycles (135 subjects), where each subject displayed a single abnormality, were compared with 79 cycles (40 subjects) in the normal group. RESULTS: For OI, subjects with a high basal FSH generally had an inadequate response with a poor chance of conception. Subjects with an abnormal BMI commonly required dosage adjustment so were more difficult to manage. Their potential for conception was normal. Older women seemed to respond normally with a normal expectation of conception. In the COS group, subjects with a moderately high basal FSH responded and conceived normally. Subjects with an abnormal BMI had an increased risk of an inadequate response leading to cancellation but if the response was adequate then the outlook was good. Older women required more gonadotrophin with a poor response and a low chance of conception. CONCLUSION: The results have better defined the anticipated responses of non-PCOS patients to gonadotrophin stimulation in both OI and COS.     

Premature luteinization is not eliminated by pituitary desensitization with leuprolide acetate in women undergoing gonadotrophin stimulation who demonstrated premature luteinization in a prior gonadotrophin-only cycle

A total of 40 women who demonstrated premature luteinization(serum progesterone 3.5 nmol/1 (1.1 ng/ml) on or before theday of human chorionic gonadotrophin (HCG) administration) duringovarian stimulation with human menopausal gonadotrophins (HMG)were restimulated in 46 subsequent cycles after pituitary desensitizationwith the gonadotrophin-releasing hormone agonist (GnRHa, 1 mg),leuprolide acetate. Five women were treated with a double doseof agonist (2 mg) when premature luteinization was determinedon the single dose protocol. In HMG-only cycles, a frank luteinizinghormone (LH) surge was detected in 30 cycles; 15 cycles werecancelled because of premature ovulation. In agonist cyclesthere were no cancellations, although 25 cycles demonstratedpremature luteinization and in six cycles a frank LH surge wasdetected. Doubling the dose of the agonist did not prevent prematureluteinization. Agonist cycles with and without premature luteinizationdid not differ in any in-vitro fertilization (IVF) outcome parameters(ampoules of gonadotrophins, day of HCG administration, peakoestradiol concentration, number of oocytes retrieved, fertilized,transferred or cryopreserved). We conclude that in patientswho demonstrate premature luteinization in a gonadotrophin-onlycycle, pituitary desensitization may not completely eliminatesubtle luteinization or a frank LH surge.