Day Of Human Chorionic Gonadotropin Administration Research Articles

Effect of ovarian stimulation on plasma lipid and apolipoprotein concentrations in a population of infertile women undergoing IVF/embryo transfer

Twenty consecutive infertile women (mean age ± SD, 36.9 ± 5.4 years) undergoing ovarian stimulation with recombinant follicle stimulating hormone (rFSH) were recruited. Serial measurements of plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), lipoprotein(a) (Lp(a)), oestradiol and progesterone were performed on day 3 before starting ovarian stimulation, on the day of human chorionic gonadotrophin (HCG) administration and on day 15 after HCG administration, respectively. The relationship between lipid and apolipoprotein concentrations and serum oestradiol and progesterone concentrations was sought. All women completed the ovarian stimulation protocol successfully. Plasma concentrations of HDL-C and Apo-A1 were significantly raised on the day of HCG administration and then returned to baseline values within 2 weeks. LDL-C, TG, Apo-B and Lp(a) were significantly increased on day 15 after HCG administration. Lp(a) variation between the first sample and the third sample correlated positively with serum progesterone concentrations ( r = 0.472, P < 0.04). No other significant correlations were found between lipid and apolipoprotein variations and either oestradiol or progesterone concentrations. It was concluded that an increase of plasma lipid and apolipoprotein concentrations deserves particular consideration and all women undergoing ovarian stimulation should be monitored for long-term atherogenic and thrombogenic risks.

Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences

Gonadotrophin-releasing hormone antagonists are effective and safe in preventing premature LH surges, a leading cause of cycle cancellation or failure during assisted conception. Two studies assessed two administration regimens for cetrorelix (as Cetrotide®): the multiple-dose (MD, 0.25 mg/day, n = 1066) and single-dose (SD, 3 mg, n = 541) protocols. Patient outcomes were very similar: >90% reached criteria for human chorionic gonadotrophin (HCG) administration and underwent oocyte retrieval; embryo transfer was performed in 83–84%; failure to retrieve oocytes was rare (0.8%); on average, 11 follicles ≥10 mm in diameter were seen on the day of HCG administration. The SD protocol was associated with higher numbers of oocytes retrieved and available for insemination, although the numbers of embryos obtained or transferred were comparable. A total of 251 and 121 pregnancies were reported in the MD and SD groups respectively. Pregnancy rates per embryo transfer were 27 and 28% respectively. Severe ovarian hyperstimulation syndrome (OHSS) occurred in <1% of cycles. Twelve per cent of patients reported local reactions to injections in the MD group, compared with 8% in the SD group; none was serious or led to discontinuation. Seventy-three per cent of patients in the SD group received only one injection. These two studies therefore show that the single-dose cetrorelix protocol offers equal efficacy and safety to the MD regimen, while having the advantage of requiring only one injection in most patients.

Higher implantation and pregnancy rates with early luteal rescue in patients undergoing in vitro fertilization (IVF) with profound estradiol (E2) drop

Objective: To evaluate whether early luteal E2 or human chorionic gonadotropin (HCG) supplementation in patients undergoing IVF cycle with profound E2 decline will affect reproductive outcome.Design: Prospective randomized study.Materials/Methods: Between January 1999 and December 2001, a total of 331 patients undergoing IVF cycles with severe early luteal E2 decline were enrolled. Serum E2 levels were measured on the day of HCG administration (E0)and day of embryo transfer(Et). Only patients with severe decline in E2 levels (E0/Et >50%) were included. They were randomized into 2 groups: Group 1 included 171 patients who received E2(n = 88) or HCG (n = 83) rescue on the day of embryo transfer. Group 2 included 160 patients who received no rescue. Downregulation was achieved with leuprolide acetate in the depot form and ovarian stimulation with recombinant FSH, human menopausal gonadotropin or combined.Results: Mean female age was 29.2 in the treated group 1 compared to 29.1 in the untreated group 2. The difference was not statistically significant (p >0.05). There was no statistically significant difference in stimulation and downregulation protocols, ampules of gonadotropin used, days of stimulation, mean number of eggs retrieved, mean number of embryos transferred and type of embryo transfer between the 2 groups. Higher implantation, ongoing and multiple pregnancy rates were achieved in group 1 (14.5%, 44.4% and 28.4%) compared to group 2 (10%,31.9% and 13.6%). The difference was statistically significant (p <0.02). There was a trend towards lower miscarriage rate in group 1 (6.2%) compared to group 2 (13.6%). The difference was not statistically significant (p >0.05). Results are shown in table I. Table IOutcome of IVF in patients with early luteal E2 decline in the treated and untreated groups.Group 1 (treated) n = 171Group 2 (untreated) n = 160Fertilization rate77.877.0Implantation rate∗The difference is statistically significant (p < 0.05).14.510.0Clinical pregnancy rate/embryo transfer47.436.9Ongoing pregnancy rate/embryo transfer∗The difference is statistically significant (p < 0.05).44.431.9Miscarriage rate6.213.6Multiple pregnancy rate∗The difference is statistically significant (p < 0.05).28.413.6∗ The difference is statistically significant (p < 0.05). Open table in a new tab Conclusions: Early supplementation with estradiol or HCG in patients with profound E2 decline may improve the reproductive outcome. Measuring serum E2 levels in the early luteal phase seems to be an important measure in the management of IVF patients.Supported by: IVF Michigan. Objective: To evaluate whether early luteal E2 or human chorionic gonadotropin (HCG) supplementation in patients undergoing IVF cycle with profound E2 decline will affect reproductive outcome. Design: Prospective randomized study. Materials/Methods: Between January 1999 and December 2001, a total of 331 patients undergoing IVF cycles with severe early luteal E2 decline were enrolled. Serum E2 levels were measured on the day of HCG administration (E0)and day of embryo transfer(Et). Only patients with severe decline in E2 levels (E0/Et >50%) were included. They were randomized into 2 groups: Group 1 included 171 patients who received E2(n = 88) or HCG (n = 83) rescue on the day of embryo transfer. Group 2 included 160 patients who received no rescue. Downregulation was achieved with leuprolide acetate in the depot form and ovarian stimulation with recombinant FSH, human menopausal gonadotropin or combined. Results: Mean female age was 29.2 in the treated group 1 compared to 29.1 in the untreated group 2. The difference was not statistically significant (p >0.05). There was no statistically significant difference in stimulation and downregulation protocols, ampules of gonadotropin used, days of stimulation, mean number of eggs retrieved, mean number of embryos transferred and type of embryo transfer between the 2 groups. Higher implantation, ongoing and multiple pregnancy rates were achieved in group 1 (14.5%, 44.4% and 28.4%) compared to group 2 (10%,31.9% and 13.6%). The difference was statistically significant (p <0.02). There was a trend towards lower miscarriage rate in group 1 (6.2%) compared to group 2 (13.6%). The difference was not statistically significant (p >0.05). Results are shown in table I. Conclusions: Early supplementation with estradiol or HCG in patients with profound E2 decline may improve the reproductive outcome. Measuring serum E2 levels in the early luteal phase seems to be an important measure in the management of IVF patients. Supported by: IVF Michigan.

Natural cycle IVF in unexplained, endometriosis-associated and tubal factor infertility.

To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF). A prospective cohort study was carried out on unexplained (33 couples), minimal peritoneal endometriosis-associated (30 couples) and tubal factor (24 couples) infertility in 223 NIVF cycles, using human chorionic gonadotrophin (HCG) for ovulation induction. During the first NIVF attempt, follicular and luteal phase oestradiol, FSH, LH and progesterone concentrations, as well as endometrial thickness and follicular diameter were similar among the three groups. Periovulatory follicular growth monitored from day of HCG administration to oocyte aspiration was significantly lowered in unexplained infertility compared with minimal endometriosis-associated and tubal factor infertility. The fertilization rate, clinical pregnancy rate per initiated cycle, per successful oocyte retrieval and per embryo transfer, in minimal endometriosis (80.0, 10.4, 16.0 and 23.5% respectively) were similar to that in tubal factor infertility patients (68.6, 5.8, 11.4 and 16.0%) but significantly higher (P < 0.05) than that of the unexplained infertility group (62.2, 2.6, 5.4 and 8.7%). The significant reduction in follicular periovulatory growth, fertilization and pregnancy rates in unexplained infertility compared with minimal peritoneal endometriosis patients may be explained by sub-optimal follicular development with possibly reduced oocyte quality, intrinsic embryo quality factors or by impaired implantation. From a clinical point of view, NIVF is less suited to unexplained infertility treatment, but might represent an interesting treatment option for minimal peritoneal endometriosis-associated infertility.

Value of serum CA-125 concentrations as predictors of pregnancy in assisted reproduction cycles.

The means by which endometrial receptivity influences conception rates in assisted reproductive technology (ART) is poorly understood. As the glycoprotein CA-125 is a product of human endometrium and is measurable in the peripheral circulation, it was investigated whether it might serve as an indicator of endometrial receptivity and predictor of pregnancy. In this prospective study, serum CA-125 concentrations of 75 ART cycles were measured 1 day before and on the day of human chorionic gonadotrophin (HCG) administration, and on the day of oocyte retrieval. These women did not have endometriosis and were induced by long-protocol gonadotrophin-releasing hormone analogue. Pregnancy was achieved in 35 (46.7%) cycles, but not in 40 cycles (53.3%). Serum CA-125 concentrations 1 day before and on the day of HCG administration and on the day of oocyte retrieval were significantly higher in cycles with pregnancy than in those without pregnancy (P < 0.05). It was noted that CA-125 concentrations on the day of oocyte retrieval were the best predictors of pregnancy, with concentrations >10 IU/ml having an accuracy of 86.6% for pregnancy. In conclusion, in intracytoplasmic sperm injection cycles, women with high serum CA-125 concentrations (>10 IU/ml) on the day of oocyte retrieval had very high pregnancy rates.

Prediction of severe ovarian hyperstimulation syndrome by free serum vascular endothelial growth factor concentration on the day of human chorionic gonadotrophin administration

In this prospective study the concentration of circulating vascular endothelial growth factor (VEGF) was followed in 10 patients with severe ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation and in 15 patients without OHSS. VEGF was assayed by means of two different commercially available kits as either free or total VEGF in serum. The concentration of free VEGF was significantly higher on the days of human chorionic gonadotrophin (HCG) administration (309.4 +/- 165.0 versus 190.3 +/- 127.8 pg/ml, P < 0.05) and embryo transfer (315.0 +/- 125.2 versus 209.3 +/- 137. 2 pg/ml, P < 0.05) in the OHSS compared to the control group. No such difference existed with respect to total circulating VEGF. In addition, there was no significant rise in the free or in the total serum VEGF concentration in the OHSS patients or the controls from the day of HCG administration up to the days of oocyte retrieval or embryo transfer. A cut-off concentration of 200 pg/ml free serum VEGF concentration on the day of HCG treatment resulted in a sensitivity of 90% and a specificity of 80% for the prediction of OHSS development. This is the first report on the parallel measurement of free and total VEGF in serum following ovarian stimulation. The value of the proposed cut-off concentration should be confirmed in a study of a larger group of women.

Colour Doppler indices of follicular blood flow as predictors of pregnancy after in-vitro fertilization and embryo transfer.

Peak systolic velocity (PSV) of individual follicles has been correlated with oocyte recovery, fertilization rate and embryo quality [in women undergoing in-vitro fertilization (IVF) and embryo transfer]. The present study assessed the role of quantitative and qualitative indices of follicular vascularity in predicting pregnancy after IVF and embryo transfer. A total of 106 women undergoing IVF treatment for infertility who were considered to be at risk of failure (>37 years of age, history of low response to gonadotrophin stimulation, or multiple failed IVF cycles) constituted the study group. PSV was measured from the three largest follicles on both the right and left ovaries on the day of human chorionic gonadotrophin (HCG) administration using an Acuson Sequoia with a 4-8 MHz transvaginal probe. The quality of follicular flow was graded from 1 to 4 according to the amount of visible colour flow around the follicle (grade 1 when one-quarter of the follicle, grade 2 when one-half, grade 3 when three-quarters, and grade 4 when the entire follicle was surrounded by colour). Clinical pregnancies resulted in 11 (10%) of the 106 high-risk women. Women who had PSV >/= 10 cm/s in at least one follicle on the day of HCG administration more often became pregnant than those with PSV <10 cm/s (P = 0.05). All pregnancies occurred in women with grade 3 or 4 follicular blood flow. Qualitative as well as quantitative measurements of follicular flow predict pregnancy after IVF and embryo transfer.

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.

Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome.

Our study compared 84 patients with polycystic ovary syndrome (PCOS) with 84 control patients who had normal ovaries and who were matched for the main determinants of success in in-vitro fertilization (IVF) and embryo transfer. Serum concentrations of oestradiol and progesterone on the day of human chorionic gonadotrophin (HCG) injection were significantly higher in PCOS than in normal patients (oestradiol 2016 +/- 1.8 pg/ml versus 1456 +/- 40.9 pg/ml, P < 0.01; progesterone 1.6 +/- 0.1 ng/ml versus 1.2 +/- 0.1 ng/ml, P = 0.03). Furthermore despite oocytes from PCOS patients having a reduced fertilization rate compared with normal patients (61.8 +/- 4.1% versus 73.5 +/- 4.3%, P = 0.03), the differences in pregnancy rate (22.6 versus 19%) and miscarriage (31.5 versus 18.7%) were not statistically significant. In PCOS patients, a critical breakpoint was identified at serum progesterone concentrations of 1.2 ng/ml on the day of HCG injection. The PCOS patients with progesterone > or = 1.2 ng/ml showed a higher pregnancy and miscarriage rate than PCOS patients with progesterone < 1.2 ng/ml (26.6 versus 17.9%, P < 0.01; and 41.7% versus 14.3%, P < 0.01 respectively). These findings suggest that premature progesterone production does not have an adverse effect on pregnancy rate in PCOS, but on the contrary, may be a predictor for success in IVF/embryo transfer.

Effect of disruption versus continuation of gonadotrophin-releasing agonist after human chorionic gonadotrophin administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization

Previous studies have described the luteolytic effect of gonadotrophin-releasing hormone agonist (GnRHa) administered in the early luteal phase. The present work was undertaken to compare in a prospective and randomized design the effect of disruption versus continuation of daily GnRHa after human chorionic gonadotrophin (HCG) administration on corpus luteum function in patients undergoing ovulation induction for in-vitro fertilization (IVF). Two different studies were designed and a total of 38 ovum donors, aged 23-30 years, were included. In the first study, the effect of GnRHa on the early luteal phase of IVF-stimulated cycles was investigated (n = 27); the patients were divided into two groups, according to whether they stopped (n = 13) or continued with daily GnRHa injections (n = 14) for an additional period of 15 days after HCG administration. Blood was drawn from luteal phase days 2 to 6 (day 0 = day of HCG administration) and oestradiol and progesterone concentrations were analysed. The second study focused on the effects of continuation versus disruption of GnRHa administration in the mid-late luteal phase. A similar design was employed including six patients who stopped GnRH on day 0 and five other women who continued GnRHa for 15 days after HCG administration. In this second study, blood was drawn from days 5 to 11 and oestradiol, progesterone and luteinizing hormone (LH) concentrations were analysed. IVF parameters were similar in both groups. The results indicate that continuous GnRHa administration, after HCG injection, does not produce changes in oestradiol, progesterone and LH concentrations in the early, mid- and late luteal phases compared to those patients in whom GnRHa is discontinued at the day of HCG administration. The present work demonstrates that, when ovulation induction is performed, the corpus luteum is driven primarily by the HCG, regardless of the administration or disruption of GnRHa in the luteal phase. This suggests that the lack of differences between continuation versus disruption of GnRHa may be due to the accumulation of the product over the previous 2-3 weeks of treatment.

Prediction of ovarian hyperstimulation syndrome by ultrasound volumetric assessment [corrected] of baseline ovarian volume prior to stimulation.

The aim of the study was to find out whether the estimation of the baseline ovarian volume prior to stimulation would be a suitable predictor for the risk of ovarian hyperstimulation syndrome (OHSS). A total of 101 patients underwent in-vitro fertilization (IVF) and embryo transfer. They had a 3-D volumetric assessment of the ovaries and body weight estimations on the first day of hormonal stimulation. A second measurement was performed on the day of ovulation induction with human chorionic gonadotrophin (HCG) together with an oestradiol 17 beta estimation in serum. During the IVF programme 15 women developed OHSS and 86 did not. There was a significant correlation between the baseline ovarian volume and subsequent occurrence of OHSS (P = 0.03). Other significant relationships were found between the occurrence of OHSS and the number of follicles (P = 0.002), the number of oocytes retrieved (P = 0.0001) and the length of the cycle (P = 0.0001). The body weight before and after the stimulation was significantly lower in the group of women who did develop the syndrome (P = 0.011 resp. 0.03). The oestradiol 17 beta concentration on the day of HCG administration in the serum of the patients who had OHSS was significantly higher (P = 0.0001). In conclusion, volumetry of the ovaries could help to detect patients at risk and prevent the occurrence of OHSS by early adjustment of the hormonal dosage. Recent advances in ultrasound technology (3-D ultrasound) enable quick and highly accurate volumetric assessments. Furthermore, our study confirms previous observations that low body weight and long cycles seem to be additional risk factors for the development of OHSS.

Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection

An ultrasonographic evaluation of the endometrium was performed in 158 patients undergoing ovarian stimulation for an in-vitro assisted reproduction programme. Endometrial thickness was evaluated in 109 patients undergoing in-vitro fertilization (IVF) for female indications and in 49 patients undergoing intracytoplasmic sperm injection (ICSI) for male indications. The maximal endometrial thickness was measured on the day of human chorionic gonadotrophin (HCG) administration by longitudinal scanning of the uterus on the frozen image using electronic callipers placed at the junction of the endometrium-myometrium interface at the level of the fundus. Cases in which the endometrial thickness was >/=10 mm were included in group A; cases in which the endometrial thickness was <10 mm were assigned to group B. The age of the patients, serum 17-beta oestradiol concentrations on the day of HCG administration, the length of follicular stimulation, the number of follicles, 17-beta oestradiol concentrations per follicle on the day of HCG and the number of embryos transferred were analysed in each case. When comparing endometrial thickness and results in IVF and ICSI patients, an endometrium <10 mm predominated in IVF patients (27.5%) compared with those undergoing ICSI (16.7%) (P = 0.05); conversely an endometrium >=10 mm was more frequent in ICSI than in IVF patients. The incidence of pregnancy was higher in IVF group A patients (32/79; 41%) than in IVF group B patients (5/30; 17%) (P = 0.03), whereas no significant difference was found between ICSI group A (13/42; 31%) and ICSI group B (3/7; 43%) patients. Thus, a higher percentage of IVF patients had thin endometrium when compared with ICSI patients; thin endometrium was a prognostic indicator of pregnancy only in the case of a female indication for infertility (IVF). A thin endometrium in cases of female infertility may reflect a previous or present uterine pathology, whereas in indications of male infertility (i.e. cases using ICSI), in the absence of any associated uterine pathology, the presence of a thin endometrium is not predictive.

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer.

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.

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

The use of gonadotrophin-releasing hormone (GnRH) agonists to control ovulation induction cycles for in-vitro fertilization (IVF) has been shown to increase the pregnancy rate and live birth rate compared with non-analogue cycles. Different formulations of GnRH agonist are available with different routes and frequencies of administration. In this prospective study, the efficacy and safety of intranasal nafarelin and buserelin as adjunctive therapy during IVF were assessed. A total of 240 female patients were recruited to the study and in the first phase patients were randomized to receive either intranasal nafarelin 200 micrograms twice daily or buserelin 200 micrograms five times daily. In the second phase, patients received either nafarelin 400 micrograms twice daily or buserelin 200 micrograms five times daily. Nafarelin 400 micrograms and buserelin 200 micrograms both produced clinical pregnancy rates of 31% per recruit and 39% per embryo transfer. The rates for nafarelin 200 micrograms were 23 and 37% respectively. There was no statistically significant difference in pregnancy rates, by either drug or dosage. The time taken for pituitary down-regulation to be achieved was significantly longer on nafarelin 200 micrograms than on either nafarelin 400 micrograms or buserelin. The total number of days stimulation with human menopausal gonadotrophin required to reach criteria for human chorionic gonadotrophin (HCG) administration was significantly longer on buserelin than on either dose of nafarelin. Median serum oestradiol concentrations on the day of HCG administration were significantly higher on either dose of nafarelin than on buserelin.

Endocrinology: A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility

The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates.

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

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

Endometrial ultrasonography as a predictor of pregnancy in an in-vitro fertilization programme.

The endometrial pattern and thickness were analysed by ultrasonography in 139 cycles stimulated for in-vitro fertilization (IVF) on the day of administration of human chorionic gonadotrophin (HCG). A semi-programmed schedule based on the pill + clomiphene citrate + human menopausal gonadotrophin (HMG) was used in all cycles. On the day of HCG administration, endometrial pattern and thickness were assessed with an Ultramark 4 (ATL) ultrasound equipped with a 5 MHz vaginal probe. Endometrial pattern I (a 'triple-line' multilayer) was observed in a total of 105 cycles (76%), and pattern II (fully homogeneous and hyperechogenic in relation to myometrial tissue) in 34 (24%). The incidence of clinical pregnancy did not differ (P = 0.52) between the groups with endometrial patterns I (23.8%) and II (29.4%). Endometrial thickness on the day of HCG administration in the group with pattern I (8.4 +/- 1.9 mm) was similar (P = 0.96) to that observed in the group with pattern II (8.4 +/- 2.0 mm). In addition, the endometrial thickness of the patients who became pregnant (8.0 +/- 1.7 mm) did not differ (P = 0.15) from that of women who did not achieve pregnancy (8.6 +/- 2.0 mm). The conclusion from the present data is that ultrasonographic analysis of endometrial thickness and refringency on the day of HCG administration had no predictive value for conception in IVF cycles.

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 > or = 3.5 nmol/l (1.1 ng/ml) on or before the day of human chorionic gonadotrophin (HCG) administration) during ovarian stimulation with human menopausal gonadotrophins (HMG) were restimulated in 46 subsequent cycles after pituitary desensitization with the gonadotrophin-releasing hormone agonist (GnRHa, 1 mg), leuprolide acetate. Five women were treated with a double dose of agonist (2 mg) when premature luteinization was determined on the single dose protocol. In HMG-only cycles, a frank luteinizing hormone (LH) surge was detected in 30 cycles; 15 cycles were cancelled because of premature ovulation. In agonist cycles there were no cancellations, although 25 cycles demonstrated premature luteinization and in six cycles a frank LH surge was detected. Doubling the dose of the agonist did not prevent premature luteinization. Agonist cycles with and without premature luteinization did not differ in any in-vitro fertilization (IVF) outcome parameters (ampoules of gonadotrophins, day of HCG administration, peak oestradiol concentration, number of oocytes retrieved, fertilized, transferred or cryopreserved). We conclude that in patients who demonstrate premature luteinization in a gonadotrophin-only cycle, pituitary desensitization may not completely eliminate subtle luteinization or a frank LH surge.

Relationship of biochemical pregnancy to pre-ovulatory endometrial thickness and pattern in patients undergoing ovulation induction

In order to assess the relationship between pre-ovulatory endometrial thickness and pattern and biochemical pregnancy, the pregnancy outcome was retrospectively analysed in 81 patients undergoing ovulation induction evaluated by vaginal ultrasound on the day of human chorionic gonadotrophin (HCG) administration or luteinizing hormone (LH) surge. Biochemical pregnancies occurred in 7/32 (21.9%) pregnancies when endometrial thickness was < 9 mm, compared to 0/49 when endometrial thickness was > or = 9 mm on the day of HCG administration or LH surge (P < 0.0025). Clinical abortions occurred in 5/32 (15.6%) pregnancies when endometrial thickness was 6-8 mm, compared to 6/49 (12.2%) when endometrial thickness was 6-8 mm (NS). Endometrial thickness was related to the cycle day of HCG or LH surge (r = 0.37, P < 0.001) but was unrelated to oestradiol level on the day of HCG administration or LH surge (r = 0.12). Biochemical pregnancies were related to endometrial pattern (r = -0.22, P = 0.02) but were unrelated to maternal age or previous abortions. Clinical abortions were related to age (r = 0.26, P = 0.01) and to previous abortion (r = 0.25, P = 0.013) but were unrelated to endometrial pattern. Neither biochemical pregnancy nor clinical abortion was related to oestradiol or LH levels on the day of HCG administration or LH surge. These findings suggest that the majority of biochemical pregnancies do not result from karyotypically abnormal embryos, as do clinical abortions.

Severe ovarian hyperstimulation syndrome in assisted reproductive technology: definition of high risk groups

In a retrospective analysis of 637 cycles of ovarian stimulation and transvaginal follicular aspiration for various assisted reproductive technologies, severe ovarian hyperstimulation syndrome (SOH) occurred in six (0.94%) cycles. The patients at a high risk of developing SOH in cycles of assisted reproduction were those who had excessive serum oestradiol levels on the day of human chorionic gonadotrophin (HCG) administration (oestradiol greater than 6000 pg/ml; 38% SOH) and a high number of oocytes obtained (greater than 30 oocytes; 23% SOH). In those patients with both oestradiol greater than 6000 pg/ml on the day of HCG administration and greater than 30 eggs retrieved, the chance of developing SOH was 80%. The higher the serum oestradiol levels and the more eggs retrieved, the higher the pregnancy rates observed. High oestradiol level did not appear to have a detrimental effect on pregnancy rates and outcome. Furthermore, our results are not consistent with suggestions that the addition of gonadotrophin-releasing hormone agonist to ovarian stimulation protocols, follicular aspiration and/or luteal support with progesterone may reduce the incidence of ovarian hyperstimulation syndrome.