Day Of Human Chorionic Gonadotropin Injection Research Articles

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome

BackgroundClinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study.MethodsA retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes.ResultsThere were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups.ConclusionCollectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

Cystic fibrosis transmembrane conductance regulator in follicular fluid and cumulus cells and its relationship with age.

Oocyte quality deteriorates with female age and numerous indicators of oocyte quality exist. In the present study, the levels of cystic fibrosis transmembrane conductance regulator (CFTR) in the follicular fluid (FF) and cumulus cells (CCs) of infertile females in 3 different age groups were assessed to determine the relationship between CFTR and female age. The general features of the 3 groups, including age, body mass index, infertility duration, basal hormone levels and the number of retrieved oocytes were compared. The FF CFTR levels of the 3 groups were also compared and multiple age-related indicators of oocyte quality were analyzed, including the estradiol levels on the human chorionic gonadotropin injection day, the morphologically normal oocyte rate and the available or high-quality embryo rate. Immunofluorescence and PCR analyses were performed to examine CFTR expression in CCs around oocytes. The results indicated differences in general features and several indicators of oocyte quality among the 3 groups and significant differences in CFTR. The FF CFTR level was positively correlated with age, which was confirmed by immunofluorescence and PCR. Collectively, these results indicated that CFTR expression in FF and CCs may be associated with oocyte quality based on the age of individuals undergoing the assisted reproduction technique.

The application of superb micro-vascular imaging in predicting pregnancy outcome in patients with in vitro fertilization-embryo transfer

Objective To investigate the role of endometrial thickness, uterine artery and spiral artery blood flow parameters, endometrial and subendometrial blood flow on pregnancy outcome in vitro fertilization-embryo transfer (IVF-ET) cycle, compare the difference of the endometrial and subendometrial blood flow typing between the superb micro-vascular imaging (SMI) and power doppler ultrasound (PDUS). Methods Forty-one patients undergoing IVF-ET cycles in our hospital were recruited in this study. Transvaginal color Doppler ultrasound was performed to determine and record endometrial thickness, peak systolic velocity(PSV), end diastolic velocity(EDV), pulse index(PI), resistance index(RI), systolic diastolic ratio(S/D) of uterine artery and spiral artery, and degree endometrial and subendometrial blood flow signals were showed under the two blood flow modes of PDUS and SMI respectively on the day of human chorionic gonadotropin(HCG) injection. The degree of the endometrial and subendometrial blood flow was scored using Applehau classification method. According to the pregnancy outcome, patients were divided into pregnancy group and nonpregnancy group, the difference of the above indicators between the two groups were compared, and the degree of endometrial and subendometrial blood flow under two kinds of blood flow mode were observed. Results ①On the day of HCG injection, patients in pregnancy group had lower RI, PI, S/D of spiral artery than those in the nonpregnancy group (P 0.05). ②On the day of HCG injection, there was significant difference between the pregnant group and nonpregnant group in endometrial and subendometrial blood flow degree with SMI mode (P=0.005). The patients with type Ⅲ in pregnancy group were most (50%). ③The endometrial and subendometrial blood flow typing (β=1.085, OR=1.085, 95% CI=1.040-8.421, P=0.042) of pregnancy group under SMI mode have an independent predictive value. With increased blood flow typing under endometrial and subendometrial blood flow, the higher the possibility of pregnancy in patients. The ROC curve analysis showed that the area under ROC endometrial and subendometrial blood flow typing SMI mode on the HCG day was 0.746(P=0.008). Conclusions SMI is a new and effective type of Doppler ultrasound technique to evaluate the endometrial and subendometrial blood flow in IVF-ET cycle. On the day of HCG injection, the endometrial and subendometrial blood flow typing in SMI mode may predict pregnancy outcomes in IVF-ET cycles, and guide to choose the best embryo transfer time. Key words: Superb micro-vascular imaging; Endometrial receptive; Embryo transfer; Pregnancy outcome

In vitro fertilization outcome in frozen versus fresh embryo transfer in women with elevated progesterone level on the day of HCG injection: An RCT

The effect of elevated progesterone level on human chorionic gonadotropin (HCG) day in in vitro fertilization cycles is controversial. Some suppose that rise in progesterone level seems to have a negative impact on implantation and pregnancy by desynchronizing the endometrium, while others disagree. To evaluate the superiority of the frozen cycle over fresh cycle on live birth in patients with elevated progesterone level on HCG day. In this double-blind, randomized clinical trial, 72 women undergoing assisted reproductive technology with elevated progesterone level (≥1.8 ng/dl) on HCG day were included. The participants were grouped by fresh versus frozen embryo transfer, randomly. Finally, the clinical pregnancy and live birth rate were compared. The implantation rate was 21.51%. The clinical pregnancy rate was 47.22% in fresh embryo transfer group (17/36) and 41.66% in frozen group (15/36) (p=0. 40). The live birth rate was not significantly difference between two groups (p=0.56). None of the fresh and frozen cycles are superior to the other and we recommend individualizing the decision for each patient. The frozen cycle may impose more emotional stress on patients.

Predicting the outcome of different protocols of invitro fertilization with anti-Muüllerian hormone levels in patients with polycystic ovary syndrome.

ObjectiveThis study evaluated associations of basal serum and follicular fluid (FF) anti-Muüllerian hormone (AMH) levels with in vitro fertilization (IVF) outcomes in polycystic ovary syndrome (PCOS) patients.MethodsThis prospective study included 179 consecutive women undergoing IVF, including 59 with PCOS and non-PCOS controls. Thirty PCOS cases had long gona-dotrophin-releasing hormone agonist (GnRH-a) and 29 had antagonist (GnRH-ant) protocols. Controls underwent conventional GnRH-a. Associations of basal serum and FF AMH levels with IVF outcomes were assessed.ResultsMedian serum and FF AMH levels, antral follicle count (AFC), oestradiol human chorionic gonadotropin injection day (peak E2), and retrieved oocyte numbers were higher in PCOS patients than in controls (all P < 0.01). Oocyte maturation and high-quality embryo rates were lower in PCOS patients than in controls (P < 0.01), but both groups had similar fertilization, implantation, clinical pregnancy, and newborn rates. Peak E2 was higher in GnRH-ant than in GnRH-a protocols (16.5 nmol/L vs. 12.1 nmol/L, P < 0.05). AMH levels were correlated with AFC in PCOS patients (P < 0.01). Peak E2 and FF AMH levels were independent predictors of oocyte number. Peak E2 predicted the fertilization rate.ConclusionSerum basal AMH levels are predictive of oocyte quantity, but not oocyte quality or IVF outcomes. Serum AMH, FF AMH, and outcomes are similar among protocols.

Impacts on thepregnancy outcome in the mice of controlled ovarian hyperstimulation treated with acupuncture at different time points

To explore the optimal time of acupuncture intervention in the assisted reproduction. One hundred and twenty female mice and 60 male mice were collected. 20 female mice were selected in the natural period group and the rest 100 female mice were prepared as the model of controlled ovarian hyperstimulation (COH). The model mice were randomized into a COH group, a down-regulation group, a gonadotropins (Gn) start group, an injection of human chorionic gonadotropin (HCG) group and an embryo culture group, 20 mice in each one. The donor mice and receptor mice were subdivided in each group, 10 mice in each subgroup. One week before the experiment, vas deferens ligature was done in 30 male mice and the other 30 male mice did not receive ligature. In the down-regulation group, the Gn start group, the HCG injection group and the embryo culture group, electroacupuncture (EA) was applied to "Guanyuan" (CV 4), "Zhongji" (CV 3) and "Sanyinjiao" (SP 6) at the time points accordingly. EA stimulation was in the condition of continuous wave, 2 Hz and 1 mA. No inter-vention was given in the natural period group and the COH group. On the day of HCG injection, the donor mice and the non-ligatured male mice were put in the same cage of each group. The fertilized ovum was collected with the date of fertilization marked and was fostered in the incubator. At the ratio of 1:1, the receptor mice and ligatured mice were put in the same cage in each group. The vaginal plug was examined in the next morning. The pseudopregnancy was marked with the date of plug observed. In the 68th hour of embryo culture, the embryo of the donor was shifted to the receptor on the same day when the plug was observed. The clinical pregnancy rate and embryo imbed site number were observed. RT-PCR assay was adopted to determine the expression of insulin-like growth factor-1 (IGF-1) mRNA in endometrium. In the COH group, the pregnancy rate, average imbed site number and endometrial IGF-1 mRNA expression were all significantly lower than those in the natural period group (all P<0.01). After EA treatment, in the Gn group, the HCG injection group and the embryo culture group, the pregnancy rates were higher significantly than those in the COH group (P<0.05, P<0.01). In the HCG injection group, the average imbed site number and IGF-1 mRNA expression were increased apparently as compared with those in the COH group (both P<0.01), better than those in the Gn group and the embryo culture group (all P<0.01). In the treatment with acupuncture combined with IVF-ET for infertility, the intervention of acupuncture on the day of HCG injection is the optimal time point. It increases the secretion of endometrial IGF-1 so as to improve the clinical pregnancy rate, the mean imbed site number and the embryo implantation.

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice

Background/Aims: To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Methods: Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. Results: No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Conclusion: Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles.

A retrospective analysis of the effect of salpingectomy on serum antiMüllerian hormone level and ovarian reserve

To determine whether previous salpingectomy is associated with serum antiMüllerian hormone (AMH) level and ovarian reserve in women under 40 years presenting for in vitro fertilization and embryo transfer. We retrospectively compared serum AMH levels measured on the ovulation induction initiation day in patients with unilateral salpingectomy, bilateral salpingectomy, and no tubal surgery, and examined the relationship with length of time after surgery and in vitro fertilization and embryo transfer parameters. A total of 198 women were included; 83 received unilateral salpingectomy, 41 bilateral salpingectomy, and 74 no tubal surgery. The baseline characteristics of the groups were similar. The mean AMH level was significantly higher in women without tubal surgery as compared with those with bilateral salpingectomy (183.48 vs 127.11 fmol/mL; P ≤ .037). The mean follicle stimulation hormone level was significantly lower in women without surgery as compared with those with bilateral salpingectomy (7.85 vs 9.13 mIU/mL; P = .048). No significant differences in duration of gonadotropin therapy, amount of gonadotropin used, estradiol level on the human chorionic gonadotropin injection day, thickness of the endometrium, number of oocytes retrieved, number of 2-pronuclei, viable embryos, and good quality embryos were found between the 3 groups. AMH level was not correlated with the number of oocytes or age in women that had undergone unilateral or bilateral salpingectomy. Salpingectomy is associated with decreased AMH level and increased follicle stimulation hormone in women seeking in vitro fertilization, though AMH level is not correlated with the number of oocytes retrieved in patients that have undergone unilateral or bilateral salpingectomy. These results suggest that salpingectomy is associated with decreased ovarian reserve.

Outcome from consecutive ICSI cycles in patients treated with recombinant human LH and those supplemented with urinary hCG-based LH activity during controlled ovarian stimulation in the long GnRH-agonist protocol

Clinical results were compared in a well-established, assisted reproduction program during the cross-over from highly purified (HP)-human menopausal gonadotropin (hMG) to rhFSH/rhLH. We included the last 33 patients treated with HP-hMG and the first 33 patients receiving rhFSH/rhLH for ovarian stimulation in their first intracytoplasmic sperm injection cycle. Patient baseline characteristics were almost identical in the two groups. Ovarian stimulation characteristics (days of stimulation, total amount of FSH administered using a modest initial loading dose of 150 IU/d, patients with oocyte retrieval) were similar for the two groups. However, the number of total and leading follicles and E2 serum levels on the human chorionic gonadotropin injection day were significantly higher in the rhFSH/rhLH group. The oocyte yield was significantly higher in the rhFSH/rhLH group as well as the number of metaphase II oocytes, difference almost reaching the statistical significance. The number of oocytes fertilized was also higher in patients receiving rhFSH/rhLH treatment. Implantation and clinical pregnancy rates were similar in both the study groups. It is concluded that in women undergoing controlled ovarian hyperstimulation under pituitary suppression for ART, the recombinant combined product containing FSH and LH in a fixed 2:1 ratio is more effective than HP-hMG in terms of follicle development, oocyte yield and quality, and fertilization rates.

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 μg corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ≥11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (Cl) 0.5−1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% Cl 1.4−2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar.

Increased responsiveness may be associated with tripronuclear embryos in both conventional in vitro fertilization and intracytoplasmic sperm injection cycles using gonadotropin-releasing hormone agonist long protocols: A self-matched observational study

In this self-matched observational study, the factors associated with the presence of tripronuclear (3PN) embryos, in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles using gonadotropin-releasing hormone agonist long protocols, were investigated. Clinical parameters were analyzed in 202 consecutive IVF-IVF or ICSI-ICSI matched cycles. The differences between the former and latter cycles were evaluated and compared according to the presence of 3PN embryos: group A [3PN (-) followed by 3PN (-)]; group B [3PN (-) followed by 3PN (+)]; group C [3PN (+) followed by 3PN (-)]; group D [3PN (+) followed by 3PN (+)]. For the IVF-IVF cycles, the E(2) on human chorionic gonadotropin injection day and the number of retrieved oocytes were increased in the 3PN (+) cycles compared to the 3PN (-) cycles of Groups B (2165.2 ± 1423.3 pg/mL vs 1468.2 ± 796.2 pg/mL, P=0.016; 10.4 ± 9.1 vs 7.2 ± 5.7, P=0.010) and C (2382.7 ± 1214.5 pg/mL vs 1553.0 ± 1119.6 pg/mL, P = 0.004; 13.1 ± 9.1 vs 9.1 ± 7.0, P < 0.001), while these outcome variables did not differ when the former and latter cycles in Groups A and D were compared. These trends were observed in the ICSI-ICSI cycles. An increased responsiveness, based on the higher E(2) and greater number of retrieved oocytes, may be associated with the presence of 3PN in both conventional IVF and ICSI cycles.

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150μg corifollitropin alfa versus daily 200IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ⩾11mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (CI) 0.5-1.8; P<0.01) and on the day of HCG injection (difference, 2.1; 95% CI 1.4-2.8; P<0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar. A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH. A total of 1509 patients were randomized in a double-blind, controlled trial to either a single injection of 150μg corifollitropin alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation. Serum levels of FSH immunoreactivity were analysed (pharmacokinetic analysis), together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response (pharmacodynamic analysis). Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards, when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached. Corifollitropin alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH. It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar.

Single dose nasal spray of gonadotropin releasing hormone (GnRH) agonist effectively matures oocytes for in vitro fertilization in an ovarian stimulation protocol using clomiphene citrate, gonadotropin, and GnRH antagonist

Objective: To investigate the efficacy of single dose nasal spray of gonadotropin releasing hormone (GnRH) agonist to mature oocytes for in vitro fertilization in a controlled ovarian stimulation protocol using clomiphene citrate, gonadotropin, and GnRH antagonist Design: Prospective, non-randomized clinical study at private clinics. Patients with repeated assisted reproduction technology failure were stimulated with clomiphene citrate, gonadotropin, and GnRH antagonist and allocated to either GnRH agonist nasal spray or intramuscular injection of human chorionic gonadotropin (HCG) for oocyte maturation. Outcome was measured by the number of oocytes retrieved and fertilized, and pregnancy rate. Materials and Methods: A total of 82 women who gave consent to receiving GnRH antagonist (Cetrorelix, Cetrotide, Serono, Switzerland) in their ovarian stimulation protocol were enrolled in the study. All patients received clomiphene citrate 100 mg/day from day 3 of menstrual period through day 7 and daily injection of 150–300 IU FSH/HMG commencing on day 4. Measurements of follicle diameter and serum E2 were initiated on menstrual day 8. When the leading follicle reached 14 mm in diameter, daily subcutaneous injection of 0.25 mg Cetrotide was initiated and continued until the day of GnRH agonist nasal spray or intramuscular HCG injection. When the leading follicle reached 20 mm in diameter, oocyte maturation was triggered by either 0.6 mg of single dose nasal spray of GnRH agonist (Buserelin, Sprecure, Aventis Pharma) (n = 40) or intramuscular injection of 10,000 IU HCG (n = 42). Oocyte retrieval was performed 36 hours after GnRH agonist/HCG administration. Only blastocysts were transferred on day 5 following oocyte retrieval. Pregnancy was defined as the visualization of gestational sac(s) at 6 weeks of gestation. Results: There was no difference in patient characteristics between the two groups. There was also no difference in the mean number of oocytes retrieved and those fertilized; 10.8 and 6.6, respectively, for the GnRH agonist group and 11.0 and 7.0 for the HCG group. Embryo transfer was possible in 38 and 39 cylces in the GnRH agonist group and HCG group, respectively, and an average of 2.2 and 2.3 blastocysts were transferred. A comparable pregnancy rate was achieved; 44.7% (17/38) for the GnRH agonist group and 53.8% (21/39) for the HCG group. Conclusion: Single dose nasal spray of GnRH agonist is as effective as intramuscular HCG injection to mature oocytes.

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.

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.

Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone.

The effect of elevated serum progesterone concentrations (> 1 ng/l) on or before the day of human chorionic gonadotrophin (HCG) injection on the outcome of women receiving gonadotrophin-releasing hormone analogue (GnRHa)/human menopausal gonadotrophin (HMG) for ovarian stimulation prior to intracytoplasmic sperm injection (ICSI) was evaluated. A total of 1275 ICSI cycles were analysed retrospectively. In 53 cycles (4.5%), serum progesterone concentrations were > 1 ng/ml. Patients in the high progesterone group had significantly higher oestradiol and luteinizing hormone concentrations on the day of HCG injection. The characteristics of the cumulus-corona cell complexes and the nuclear maturity of the oocytes were similar in the groups of patients with high and low serum progesterone levels. Fertilization and cleavage rates as well as embryo quality were not different in the two groups. No difference in implantation or clinical pregnancy rates was observed between the high progesterone and low progesterone groups. Moreover, the cumulative exposure to progesterone during the follicular phase, as expressed by the area under the curve (AUC), and the duration of exposure to high serum progesterone levels (> 1 ng/ml) were not significantly different between pregnant and non-pregnant women in the high progesterone group. We conclude that in ICSI cycles pretreated with GnRHa, increased serum progesterone concentrations on or before the day of HCG injection do not affect ICSI outcome.

Implantation: Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients

This study was undertaken to investigate an empirical observation that 'high responder patients have poorer in-vitro fertilization (IVF) outcome than normal responder patients'. The aim of our study was to analyse the effect of high serum oestradiol and progesterone concentrations at the day of human chorionic gonadotrophin (HCG) administration on endometrial receptivity and oocyte-embryo quality in high and normal responder patients. The IVF patients were divided into two groups: 59 high responder patients who voluntarily donated some of their oocytes, and a control group consisting of 105 normal responder patients. Both groups were compared in terms of the number and quality of oocytes retrieved, embryos transferred, fertilization, implantation and gestation rates, serum oestradiol and progesterone concentrations and the oestradiol:progesterone ratio on the day of HCG injection. To ascertain oocyte-embryo quality, a second control group of 96 women undergoing oocyte donation (receiving oocytes from high responder patients) was considered. To assess the impact of steroid concentrations on endometrial receptivity, high responder patients were divided into two subgroups according to oestradiol concentration, above or below the minimal oestradiol and progesterone concentrations (mean--SD) in this group. The normal responder patients were divided into two subgroups according to oestradiol concentration, above or below the maximal oestradiol and progesterone concentrations (mean+SD) in this group. To assess further the relevance of oestradiol concentration on endometrial receptivity, patients were divided into different subgroups according to increasing oestradiol concentration, regardless of whether they were high or normal responders. High responder patients had significantly decreased implantation and pregnancy rates per cycle compared with normal responder patients (33.3 versus 16.3 and 11.1 versus 5.4% respectively; P < 0.05). The results of 108 embryo transfers in 91 recipients who received oocytes from the high responder group showed normal embryo quality. Implantation rates and pregnancies per cycle were significantly lower in high responder patients with serum oestradiol concentrations > 1700 pg/ml compared with those having oestradiol concentrations < or = 1700 pg/ml, as well as in normal responder patients with serum oestradiol concentrations > 2200 pg/ml compared with those having oestradiol concentrations < or = 2200 pg/ml. Considering all the patients together, significant decreases in pregnancy and implantation rates were observed when oestradiol concentrations were > 2500 pg/ml compared with patients having lower oestradiol concentrations. Our clinical results demonstrate that high serum oestradiol concentrations on the day of HCG injection in high and normal responder patients, regardless of the number of oocytes retrieved and the serum progesterone concentration, are detrimental to uterine receptivity without affecting embryo quality.

Programming of ovarian stimulation with norethindrone acetate in IVF/GIFT cycles

Twenty patients were given norethindrone acetate (NET) to program the initiation of controlled ovarian hyperstimulation and to coordinate follicular aspiration with surgery to obtain spermatozoa from the husband. Patients received NET, 10 mg/day orally, starting between days 2 and 4 of the cycle. The duration of NET therapy varied from 9 to 37 days. The mean time of onset of vaginal bleeding, after cessation of NET, was 2.9 +/- 0.7 days. Ovarian stimulation was carried out with a combination of a luteinizing hormone releasing hormone analog, follicle-stimulating hormone and human menopausal gonadotrophin. The day of human chorionic gonadotrophin (HCG) administration ranged from day 8 to day 15 of the cycle (10.1 +/- 1.7). On the day of HCG injection, the mean E2 level was 2188 +/- 1126. The mean number of follicles aspirated was 18.4 +/- 9.9 per cycle. The mean number of oocytes collected per cycle was 15.5 +/- 8.5. There was no correlation between duration of NET suppression and the number of days of gonadotrophin therapy needed to reach HCG administration. The large number of oocytes retrieved is probably related more with the fact that the patients represented a group with a purely male factor of infertility, than by the specific drug protocol utilized. Our results demonstrate that the ovarian response to gonadotrophin stimulation was not affected by NET administration. The main advantages of the use of this drug for cycle control are that its administration is oral, simple and inexpensive.