Day Of Human Chorionic Gonadotropin Administration Research Articles

Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH) co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated with pregnancy outcome. Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonist and recombinant FSH with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late-follicular-phase LH concentration also showed a significant positive association with progesterone concentration ( P = 0.018). Administration of rLH during ovarian stimulation did not affect progesterone concentration. The present study does not support an association between progesterone concentration on the day of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment. Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH concentration. The present study evaluates whether the sex steroid progesterone produced by the granulosa cells of the developing follicle reflects the likelihood of whether a woman undergoing stimulation with exogenous hormone preparations will achieve pregnancy. The study was unable to demonstrate any association between the progesterone concentration close to ovulation and the chance of conceiving. However, the study found a close association between the number of follicles that developed and the concentration of progesterone at the end of the stimulation period, suggesting that each individual follicle contributed to the circulating progesterone concentration around the time of ovulation. A significant association was found between the pituitary-derived hormone LH and the progesterone concentration, suggesting that LH stimulated progesterone secretion by the follicle.

Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women in the reproductive age group, and is one of the most common causes of hyperandrogenic anovulatory infertility. The aromatase inhibitor, letrozole, has been used for induction of ovulation. The purpose of this study was to compare the effects of letrozole and clomiphene citrate in induction of ovulation among patients with PCOS undergoing intrauterine insemination.MethodsIn a double-blind randomized study, 60 infertile patients with PCOS received standard doses of either clomiphene citrate or letrozole as an induction protocol prior to intrauterine insemination. A hormonal profile, pelvic ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients. The patients were monitored for ovulation by translational ultrasonographic folliculometry, with measurement of number and size of the follicles, as well as endometrial thickness. Human chorionic gonadotrophin (HCG) was injected intramuscularly when at least one mature follicle ≥18 mm diameter was detected, and intrauterine insemination was performed 32–36 hours later. Transvaginal ultrasound and β-HCG measurement were performed for confirmation of pregnancy.ResultsLetrozole and clomiphene citrate achieved follicle maturation within a mean ± standard deviation (SD) of 13.2 ± 1.53 and 14.1 ± 1.35 days, respectively, showing no significant difference (P > 0.05). The mean number of follicles reaching ≥18 mm on the day of HCG administration was significantly higher in patients who received clomiphene citrate (2.9 ± 1.77) than in those receiving letrozole (1.2 ± 0.9). Letrozole had a significantly greater effect than clomiphene citrate on endometrial thickness (9.16 ± 1.36 versus 4.46 ± 1.71). The number of pregnancies achieved in the letrozole group was significantly (P < 0.05) greater than in the clomiphene group.ConclusionLetrozole in patients with PCOS is as effective as clomiphene citrate in inducing ovulation, and although the number of follicles produced by induction with letrozole were less than those produced by clomiphene, letrozole had a significantly greater effect on endometrial thickness than clomiphene citrate, and the incidence of pregnancy after intrauterine insemination was significantly higher, with a lower incidence of multiple pregnancy.

Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression

Premature progesterone rise during gonadotrophin-releasing hormone (GnRH) antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. This study evaluated endometrial gene expression on the day of oocyte retrieval according to the concentration of serum progesterone on the day of human chorionic gonadotrophin (HCG) administration in GnRH-antagonist/recombinant FSH IVF cycles with fresh embryo transfer. Endometrial biopsies ( n = 14) were analysed with Affymetrix HG U133 Plus 2.0 Arrays. Patients were divided into three groups according to their progesterone serum concentration on the day of HCG administration: ⩽0.9 ng/ml (group A), 1–1.5 ng/ml (group B) and >1.5 ng/ml (group C). Gene expression analysis showed a small number of significantly differentially expressed probe sets between groups A and B (five up/23 down in B) and a large difference between groups B and C (607 up/212 down; P ⩽ 0.05, fold change ⩾1.4). Validation was performed with quantitative real-time PCR on selected genes. As far as is known, this is the first study to demonstrate a distinct difference in endometrial gene expression profile between patients with a progesterone serum concentration above and below the threshold of 1.5 ng/ml on the day of HCG administration. During an IVF treatment in a stimulated cycle, some patients undergo an early elevation of progesterone during the follicular phase of their menstrual cycle. This is associated with lower pregnancy and implantation rates. In this study, we evaluated endometrial gene expression on the day of oocyte retrieval according to the concentration of serum progesterone on the day of human chorionic gonadotrophin (HCG) administration in stimulated IVF cycles with fresh embryo transfer. Fourteen endometrial biopsies were divided into three groups according to their progesterone serum concentration: ⩽0.9 ng/ml (group A), 1–1.5 ng/ml (group B) and >1.5 ng/ml (group C). Microarray gene expression analysis showed a small difference between groups A and B and a large difference between groups B and C. Technical validation with a more quantitative PCR technique was performed on selected genes. As far as is known, this is the first study to demonstrate a distinct difference in endometrial gene expression profile between patients with a progesterone serum concentration above and below the threshold of 1.5 ng/ml on the day of HCG administration, which might reflect an important issue for implantation failure in IVF patients with premature progesterone rise.

Effects of body mass index and age on the treatment of in vitro fertilization-embryo transfer among patients with non-polycystic ovarian syndrome

To investigate the impacts of body mass index (BMI) and age on in vitro fertilization-embryo transfer (IVF) and intracytoplasmic sperm injection (ICSI) treatment in infertile patients without polycystic ovary syndrome (PCOS). A retrospective study of 1426 patients during Jun. 2001 - Nov. 2009 was carried out. Multiple regression was used to analyze the effects of BMI (low weight: BMI < 18.5 kg/m(2), normal weight: BMI 18.5 - 23.99 kg/m(2) and over weight-obesity: BMI ≥ 24 kg/m(2)) and age (young: 20 - 34 years old, eld: 35 - 45 years old) on controlled ovarian stimulation (COH) [including: dose and duration of Gn, E2 level on day of human chorionic gonadotropin (HCG) administration, number of oocytes collected and full-grown follicles], number of fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos and clinical pregnancy outcome. (1) Gn dose for the patients whose age were 35 and the above, had a positive correlation with age (P < 0.001), 12.70% of the total variation of Gn dose was related to age (standardized partial regression coefficient was 0.343). (2) Estradiol level on day of HCG administration had a negative correlation with BMI in overweight-obesity patients, and so were the patients whose age were 35 and above (P value respectively lower than 0.037 and 0.018). 0.80% of the total variation of estradiol (HCG day) is related to age and overweight-obesity while age took greater proportion (standardized partial regression coefficients were 0.066 and 0.058 respectively). (3) For older patients, age appeared to have negative relationships with duration of Gn and number of oocytes collected, full-grown follicles, fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos (P < 0.05). (4) Compared to young-normal weight patients, the odds ratio of pregnancy in eld-low weight and eld-overweight-obesity patients were 0.482 and 0.529 (P < 0.05) respectively. Age, but not the BMI, had significant effects on IVF/ICSI treatment. It seems that factors as losing weight before IVF or ICSI treatment effective in reducing the dose of Gn.

Role of the endocrine profile for the achievement of pregnancy with IVF

The predictive value of pre-ovulatory hormones for achievement of pregnancy has been extensively evaluated in assisted reproductive technologies. Currently, no high-quality evidence exists to support or deny an association between oestradiol levels on the day of human chorionic gonadotrophin (HCG) administration and pregnancy achievement in IVF cycles. Retrospective studies appear to support the lack of such an association. Progesterone elevation on the day of HCG administration does not appear to be associated with the probability of clinical pregnancy in women undergoing IVF. Finally, no retrospective studies exist to suggest that low endogenous midfollicular LH concentrations are associated with a significantly decreased probability of ongoing pregnancy beyond 12 weeks of gestation in IVF. In two prospective studies, high endogenous LH concentrations during down-regulation were associated with a decreased probability of ongoing pregnancy beyond 12 weeks of gestation. Existing studies evaluating the association between single measurements of pre-ovulatory hormones and the achievement of pregnancy are of low quality and cannot lead to solid conclusions. Based on the available literature, it appears that no association exists between single assessments of oestradiol, progesterone or LH, and pregnancy achievement.

Randomized controlled pilot trial of luteal phase recombinant FSH stimulation in poor responders

This study investigated whether luteal phase initiation of FSH supplementation would improve oocyte yield compared with follicular phase administration in women with poor ovarian response (POR). A two-arm, randomized, open-label pilot trial was performed at a university-based infertility centre. In nine of 18 infertile women with a history of POR in a previous cycle [<5 follicles on day of human chorionic gonadotrophin (HCG) administration; <5 oocytes retrieved; previous IVF cycle cancellation due to POR] FSH was administered during the mid-luteal phase of the preceding menstrual cycle. The primary outcome measure was the number of oocytes retrieved. Secondary endpoints included: follicles >10 mm and >16 mm and oestradiol concentration on the day of HCG administration, peak oestrogen concentration, pregnancy and live birth rates. All endpoints comparing luteal versus follicular stimulation were similar. In paired analysis of patients in the luteal arm compared with the prior cycle, there was a significant increase in days of stimulation ( P = 0.01) and number of follicles >10 mm ( P = 0.02) and >16 mm ( P = 0.02) on day of HCG administration. IVF outcomes with luteal phase FSH compared with follicular phase FSH were similar. Luteal phase initiation of FSH is a safe and potential alternative protocol in poor responders.

Serum progesterone concentration on day of HCG administration and IVF outcome

To determine the relationship between serum progesterone on the day of human chorionic gonadotrophin (HCG) and the pregnancy outcome of IVF–embryo transfer treatment, 251 infertile patients undergoing IVF–embryo transfer with gonadotrophin-releasing hormone agonist (GnRHa) and recombinant FSH (rFSH) were prospectively studied. Among them, 118 patients underwent 118 cycles of frozen embryo transfer (FET) treatment, one cycle per patient. All the cycles were grouped according to serum progesterone concentration on the day of HCG administration (<3.97 nmol/l or ≥3.97 nmol/l). The incidence of progesterone elevation was 36.7% (92/251), and in this group the pregnancy rate was significantly lower (25.97 versus 48.57%; P < 0.001). If the serum progesterone on the day of HCG was over 6.0 nmol/l, their pregnancy outcome was much poorer (13.79 versus 44.68%). However, the pregnancy rate was similar in FET cycles whether the serum progesterone was over 3.97 nmol/l (34.00 versus 36.76%) or 6.0 nmol/l (42.86 versus 34.02%). In conclusion, serum progesterone on the day of HCG may predict IVF pregnancy outcome. The higher serum oestradiol and progesterone concentrations may affect endometrial receptivity. For patients with an extremely high progesterone concentration on the day of HCG (such as over 6.0 nmol/l), transfer of frozen embryos in a natural cycle is suggested.

Study on relationship between perifollicular blood flow and in vitro fertilization-embryo transfer

Objective To study the relationship between perifollicular blood flow and follicule development, oocyte maturing rate, fertilizing rate, cleaving rate, embryo quality and the outcomes of embryo transfer. Methods The samples were selected from 66 suffers who underwent in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI). Eeach patients' perifollicular blood flow(diameter ≥ 12mm)was estimated on the day of human chorionic gonadotropin(HCG)administration. Results Among 66 cycles,26(39.4%) cycles resulted in pregnancy. perifollicular blood flow resistance index(RI), peak systolic velocity/end diastasis velocity(S/D) of non-pregnant group was significantly higher than that of the pregnant group( P <0.004). When RI < 0.49, the pregnancy rates, fecundation rates, fertilization rates, metaphase numbers for the of second meiosis oocytes increased evidently( P <0.05), but there were no statistical difference in gonadotropin dosage, cycle frequency, infertility years, ages, estradiol(E2)on the day of HCG administration, numbers of oocyet retrieved and high-quality embryo rates( P >0.05). There were no statistical difference between non-pregnant group and pregnant group in S and D ( P >0.05). There was no correlation between periFollicular blood flow RI and follicular diameter by linear regression analysis. Conclusion Our study shows that perifollicular blood flow RI and S/D are effective indices of predicting the pregnancy outcome of IVF-ET.

Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity to implantation

In IVF programmes, transvaginal ultrasonography is used as a non-invasive method to evaluate uterine receptivity. The aim of this study was to determine when to perform this investigation in order to optimize prediction of the likelihood of pregnancy. Over 9 months, 124 patients undergoing IVF or intracytoplasmic sperm injection were studied. The ultrasonographic evaluation included endometrial thickness, endometrial pattern, uterine artery pulsatility index, protodiastolic notch, end-diastolic blood flow, and endometrial–subendometrial blood flow distribution pattern. All patients underwent ultrasonographic investigation on the days of human chorionic gonadotrophin (HCG) administration, oocyte retrieval, and embryo transfer. Statistical analysis was done using recursive-partitioning analysis. The pregnancy and implantation rates per transfer were 33 and 19.8% respectively. In terms of single parameters, women with an end-diastolic blood flow, an endometrial–subendometrial blood flow and a multilayered endometrium were more likely to be pregnant than women without one or more of these signs. The most effective combination for evaluation of uterine receptivity was end-diastolic blood flow, endometrial pattern and endometrial thickness. Sensitivity and specificity of this combination were around 81%, positive predictive value was 68.2%, and negative predictive value 89.7%. The best sensitivity and specificity were obtained on the day of HCG administration: respectively 81.1 and 81.3%.

Steroid receptor expression in the human endometrium during the follicular phase of stimulated cycles

To assess steroid receptor expression in human endometrium at different days during the follicular phase in stimulated cycles. Prospective randomized study. Thirty women <39 years of age with basal levels of estradiol <80 pg/ml and progesterone <1.6 ng/ml, have been so far included in this study. All women received 100 IU/day of recombinant follicle stimulating hormone, starting on day 2 of the cycle. Addition of gonadotropin releasing hormone antagonists was performed as soon as a follicle of 12 mm was present, while human chorionic gonadotropin (HCG) was administrated as soon as a follicle of 18 mm was present. Ultrasound-guided aspirational biopsy of the endometrium was performed on the first day after the end of menstruation (day 0) in all women. According to random allocation, a second biopsy was performed two (Group 0 + 2, n = 10) or four (Group 0 + 4, n = 10) days after the first biopsy or on the day of HCG administration (Group 0 + HCG, n = 10). The immunohistochemical signal of estrogen receptor (ER)-alpha and both progesterone receptor (PR) isoforms in epithelial cells from the endometrial glands and in stromal cells was recorded and graded as either absent, weak, moderate or strong (0 to 3 scale). 1000 stromal and 1000 glandular cells were examined in each sample and a mean score was produced (range: 0–3). Difference in receptor expression between the two biopsies performed in each group is expressed as median difference (MD) in intensity of staining. ER expression did not significantly change in the 0 + 2 group (stroma: MD = −0.08, P=0.46; glands: MD = 0.04, P=0.92), the 0 + 4 group (stroma: MD = 0.13, P=0.6; glands: MD = 0.01, P=0.92) and the 0 + HCG group (stroma: MD = 0.08, P=0.89; glands: MD = −0.01, P=0.89). On the contrary, PR expression was significantly increased in the 0 + 2 group in both glands (MD = 0.16, P=0.04) and stroma cells (MD = 0.19, P=0.03). In addition, a significant increase in PR expression was present in group 0 + 4 in the stroma (MD = 0.16, P=0.03) but not in glandular cells (MD = 0.25, P=0.09). Finally, PR expression was significantly increased in the 0 + HCG group (stroma: MD = 0.39, P=0.04; glands: MD = 0.53, P=0.03). Estradiol receptor expression appears to remain stable throughout the duration of the follicular phase in stimulated cycles. However, progesterone receptor expression is significantly increased already two days after the end of menstruation in both stromal and glandular cells and remains significantly increased on the day of HCG administration.

Age, oestradiol and blastocysts can predict success in natural cycle IVF–embryo transfer

The aim of this study was to evaluate the influence of maternal age and oestradiol concentrations on blastocyst development and live birth rates in natural cycle IVF–embryo transfer. This observational study included 397 natural cycles with IVF–embryo transfer for female infertility with embryo transfer on day 5. The cycles were divided into two groups according to the woman's age (<39 and ≥39 years of age), and into two groups according to oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (0.4–0.49 nmol/l and 0.5–1.2 nmol/l). Comparison between the cycles in younger versus older age groups showed significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (55 versus 29%, 23 versus 3% and 13 versus 2% respectively) (P < 0.001). Comparison between cycles with lower versus higher oestradiol concentrations showed no significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (47 versus 49%, 18 versus 18%, and 11 versus 10% respectively). Advanced maternal age negatively predicts the success of natural cycle IVF, while low oestradiol concentrations on the day of HCG administration (ultrasound criteria fulfilled) do not negatively predict blastocyst development and success of natural cycle IVF.

P-149: Peak serum estradiol (E2) is a predictor of pregnancy outcome in in vitro fertilization (IVF)

To determine whether peak serum E2 at time of human chorionic gonadotropin (HCG) administration during IVF cycle is predictive of pregnancy outcome. Retrospective study of patients at a private IVF clinic who underwent IVF utilizing standard leuprolide long protocol. The medical records of 230 IVF patients who underwent controlled ovarian hyperstimulation utilizing standard leuprolide long protocol were reviewed from January 1, 2003 to December 31, 2005. HCG was administered when at least 2 follicles were at least 18 millimeter (mm) and at least 50% were 14 mm or greater. Patients were stratified into 5 peak E2 categories (less than 1000 picogram/milliliter (pg/ml), 1000-2000 pg/ml, 2001-3000 pg/ml, 3001-4000 pg/ml and over 4000 pg/ml) at time of HCG administration. Logistic regression models were used to examine the associations with age, cycle day 3 (CD3) follicle stimulating hormone (FSH), history of IVF failure, number of embryos transferred (ET), implantation rate, and on-going pregnancy rates. Multivariate analysis revealed that compared with peak E2 levels over 4000 pg/ml, the under 1000 pg/ml (Odds Ratio (OR), 0.29; 95% Confidence Interval (CI), 0.09, 0.94), 1001 to 2000 pg/ml (OR, 0.43, 95% CI, 0.18, 0.98), and 3001 to 4000 pg/ml (OR, 0.28, CI, 0.11, 0.71) groups were significantly less likely to have an on-going pregnancy. As age increased (5 year increments from age 24 years) they were less likely to become pregnant (OR, 0.49, CI, 0.34, 0.73), p < 0.001. An increase in the number of embryos transferred (ET) was associated with a significantly higher on-going pregnancy rate (OR 1.47, CI 1.03, 3.09), p<0.05. CD3 FSH levels and previous history of IVF failure were not associated with a higher on-going pregnancy rate. Our findings show that higher peak E2 levels on day of HCG administration can serve as a reliable predictor of positive pregnancy outcomes in patients undergoing IVF.

WITHDRAWN: Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction cycles.

Until recently, the main source of exogenous follicle stimulating hormone (FSH) for therapeutic use in infertility had been the urine of postmenopausal women. New developments have resulted in the production of FSH in vitro by recombinant DNA technology. The extremely high purity and batch-to-batch consistency of recombinant FSH (rFSH) make it an attractive alternative to urinary FSH (uFSH). To conduct a systematic review and meta-analysis of randomised trials comparing the effectiveness of rFSH with uFSH in ovarian stimulation protocols in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) treatment cycles. Search strategies included on-line searching of the MEDLINE and EMBASE databases from 1985 to 1999, hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings, peer consultation and contacting the pharmaceutical companies that manufacture the gonadotropins under consideration. Randomised trials comparing rFSH with uFSH for ovarian stimulation in IVF or ICSI treatment for infertility. The main outcome measure was clinical pregnancy per cycle started. Also considered were clinical pregnancy per cycle reaching oocyte retrieval and per cycle reaching embryo transfer (ET), ongoing pregnancy per cycle started, spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, total dose of FSH, and number of oocytes retrieved. Common odds ratios (OR) and risk differences for rFSH relative to uFSH were calculated after testing for homogeneity of treatment effect across all trials. The fixed effects model was used, unless significant heterogeneity was present, in which case the random effects model was used. The overall odds ratio for clinical pregnancy per cycle started was 1.21 (95% confidence limits (CL) 1.04,1.42) for rFSH compared to uFSH. The risk difference was a 3.7% (0.8,6.7) absolute increase in clinical pregnancy rate with rFSH. The OR for ongoing pregnancy per cycle started was 1.29 (1.08,1.54). There was no significant difference between rFSH and uFSH in the rates of spontaneous abortion, multiple pregnancy or OHSS. The total dose of FSH was lower by 406 (185,627) IU with rFSH, but there was no significant difference in the number of follicles or serum estradiol on hCG day or in the number of oocytes retrieved. This review has demonstrated a statistically significant increase in clinical pregnancy rate with rFSH compared to uFSH, when used for ovarian stimulation in assisted reproduction. This benefit was observed only in standard IVF cycles and not in cycles in which ICSI was used.

Homologous intrauterine insemination in controlled ovarian hyperstimulation cycles: A comparison among three different regimens

Objective The objective was to assess the efficacy of double intrauterine insemination (IUI) over a single periovulatory IUI in patients undergoing controlled ovarian hyperstimulation with low-dose recombinant follicle stimulating hormone (rFSH) combined with human chorionic gonadotropin (HCG). Study design Ninety-four infertile women were randomly assigned to three groups; in group A (38 patients, 47 cycles) a single IUI was performed 36 h after HCG administration combined with timed intercourse the day of HCG administration; within group B (43 patients, 48 cycles) IUI alone was performed 36 h after HCG administration; in group C (39 patients, 43 cycles) a double IUI 12 and 36 h after HCG administration was performed. Results The mean age and the causes of infertility were similar between the three groups. The number of follicles greater than 15 mm on the day of HCG administration and the overall dose of rFSH required per cycle was not significantly different among the groups. The pregnancy rate (PR) per cycle and per patient was 14.9% and 18.4% in group A, 10.4% and 11.6% in group B, 20.9% and 23.1% in group C, respectively. There was no statistically significant difference in PR among the three groups. Conclusion In rFSH/HCG cycles, two IUIs performed 12 and 36 h after HCG administration do not significantly improve pregnancy rates over a single insemination performed 36 h after HCG administration combined with or without timed intercourse the day of HCG administration.

A Study Comparing the Effects of Two Follicle-Stimulating Hormones used in Assisted Reproductive Technique

To compare the efficacy of recombinant follicle-stimulating hormone (rFSH) and highly-purified urinary follicle-stimulating hormone (uFSH HP) used in in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment. 76 patients undergoing in-vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI) treatment were divided into rFSH group (n=38) and uFSH HP group (n=38) randomly. Two groups were used rFSH and uFSH HP respectively after the pituitaries were down regulated with Gonadotropin releasing hormone agonist (GnRH-a). Human chorionic gonadotrophin (HCG) were injected intramuscularly when the diameter of the dominant follicle were more than 18mm, and IVF/ICSI were treated after 36 hours of oocytes retrieval. The embryos were transferred 2 days later. The results were observed including the number of ampoules, follicles and oocytes retrieved, serum estradiol level, the fertilization rate, the pregnancy rates and the rate of complications. There were significant difference in the number of ampoules between rFSH group (34.50±7.87) and uFSH HP group (40.47±9.22) (P<0.05). The total doses of rFSH group was lower than those of uFSH HP group[2587.50±590.23IU vs. 3035.53±691.30IU (P<0.05)]. There were no significant difference in the number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, and number of oocytes retrieved. The fertilization rate was higher in rFSH group(87.18%) than in uFSH HP (73.65%)(P<0.05). The pregnancy rates were 36.8% and 26.3% for each group respectively. No differences were found in the number of spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), and the weeks and the weights of the infants(P>.05). rFSH produced higher fertilization rate and pregnancy rate than uFSH, and the total dose required was lower. It was a more efficiency and save follicle stimulating hormone, and more suitable for clinical application.

Intraobserver and Interobserver Reproducibility of Ovarian Volume, Antral Follicle Count, and Vascularity Indices Obtained With Transvaginal 3-Dimensional Ultrasonography, Power Doppler Angiography, and the Virtual Organ Computer-Aided Analysis Imaging Pr

The purpose of this study was to assess intraobserver and interobserver reproducibility of the parameters of ovarian response and oocyte ability, studied by 3-dimensional ultrasonography and power Doppler angiography (PDA), and the possible influence of the ovarian functional stage. Twenty-nine women were included in an in vitro fertilization program. Fourteen women were evaluated after pituitary suppression (basal group), and 15 were scanned on the human chorionic gonadotropin administration day, after gonadotropin ovarian stimulation (stimulated group). A first observer acquired 2 volumes for each ovary. Another observer performed a second analysis of the volumes acquired by the first observer. We analyzed ovarian volume, follicle number in the basal group, vascularization index, flow index, and vascularization-flow index. The volumes were processed by the Virtual Organ Computer-Aided Analysis imaging program using plane A and 15 degrees rotational steps. Ovarian volume showed excellent intraobserver and interobserver agreement, with an intraclass correlation coefficient (Intra-CC) and an interclass correlation coefficient (Inter-CC) close to the unit. The Intra-CC and Inter-CC about the number of follicles were 0.964 and 0.978, respectively. Vascularity indices showed an Intra-CC greater than 0.90. The vascularization index and the vascularization-flow index showed higher interobserver than intraobserver reproducibility (Inter-CC > 0.96 for both). The flow index Inter-CC was 0.898. The reproducibility differences between the basal and stimulated ovary measurements were not significant. There is an excellent intraobserver and interobserver reproducibility of the ovarian volume, follicle counts, and 3-dimensional PDA indices. The ovarian functional stage has no influence on the reliability. Three-dimensional ultrasonography and PDA improve the study of ovarian parameters, and their reliability impels a change in the current clinical routine of performing and interpreting ultrasonography.

Premature luteinization defined as progesterone estradiol ratio >1 on hCG administration day seems to adversely affect clinical outcome in long gonadotropin-releasing hormone agonist cycles.

To examine the effect of premature luteinization on the outcomes in long gonadotropin-releasing hormone agonist cycles. Two-hundred and forty-eight patients who had undergone assisted reproductive technology for infertility treatment between 2001 and 2002 were enrolled into the study. The patients were separated into two groups according to P/E2 ratios on human chorionic gonadotropin administration day. Group A consisted of the patients whose P/E2 ratio was 1 (n = 116) and Group B consisted of the patients with premature luteinization of which P/E2 ratio was > 1 (n = 132). The P/E2 ratio calculation was performed as follows: P (in ng/mL) x dagger 1,000/E2 (in pg/mL). The primary outcome measures included oocyte quality, fertilization rates and clinical pregnancy rates. The mean number of mature oocytes retrieved in the groups were 9.5 +/- 4.8 and 6.4 +/- 3.6, respectively, and the difference was statistically significant (P < 0.05). Although the difference between the fertilization rates in Group A and Group B was not statistically significant (P > 0.05), the clinical pregnancy rates seemed to be affected adversely in the Group B patients with premature luteinization (41.4%versus 28%, respectively; P < 0.05). Premature luteinization, defined as P/E2 > 1 on human chorionic gonadotropin administration day, in long gonadotropin-releasing hormone agonist cycles seems to adversely affect clinical outcome.

Serum progesterone concentrations on the day of HCG administration cannot predict pregnancy in assisted reproduction cycles

The effect of subtle rises of progesterone in the late follicular phase of cycles of ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonists on pregnancy outcome is controversial. This study used receiver-operating characteristic (ROC) analysis to gain further insight into the predictive value of serum progesterone concentrations on the day of human chorionic gonadotrophin (HCG) injection in normally responding patients receiving the long protocol of GnRH agonist (group L; n = 218) and in low responders receiving the short (‘flare-up’) protocol (group S; n = 159). ROC analysis showed that serum progesterone concentration on the HCG day was not indicative of conception and non-conception cycles in the whole population studied, in group L or in group S. To further assess the potential impact of ‘high’ concentrations of circulating progesterone on the day of HCG administration on pregnancy rates and outcome, the threshold value (<0.9 ng/ml) to discriminate between women with ‘high’ (group H; n = 197) and ‘normal’ (group N; n = 180) progesterone was applied. No significant differences were found with respect to pregnancy and miscarriage rates between these two groups. Serum progesterone concentrations on the day of HCG administration therefore cannot predict pregnancy in assisted reproduction cycles using GnRH agonists and gonadotrophins.

Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist administration: randomized controlled trial

A significantly lower pregnancy rate following the gonadotrophin-releasing hormone (GnRH) antagonist protocol as compared with the long GnRH agonist protocol has been reported. The objective of this study was to investigate whether increasing the dose of gonadotrophins on the day of antagonist administration would increase the pregnancy rate. This study is an open labelled, randomized controlled trial and allocation was done using sealed envelopes. One hundred and fifty-one subfertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles were included in the study. Ovarian stimulation was started on day 3 of the cycle, using 150–300 IU human menopausal gonadotrophin (HMG)/day. From day 8 onward, daily vaginal ultrasound and daily urinary LH estimation were performed. If a premature LH rise was detected, the cycle was cancelled. The antagonist (0.25 mg daily) was started when the leading follicle reached 15 mm in mean diameter and LH testing in urine was negative up to and including the day of human chorionic gonadotrophin (HCG) injection. Patients were randomized on the day of starting the antagonist into two groups: group A, 72 patients with no increase in HMG dose, and group B, 79 patients in whom the dose of HMG was increased by 75 IU on the day of antagonist administration, and continued till the day of HCG administration. The results showed no statistically significant difference between the groups regarding number of oocytes retrieved, embryos obtained, implantation rate, clinical pregnancy rate and multiple pregnancy rate. It was concluded that there is no clinical evidence for increasing the dose of HMG on the day of antagonist administration.

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.