Day Of hCG Administration Research Articles

Does thalassemia influence ovarian response? An analysis of 127 cycles involving pre-implantation genetic diagnosis of thalassemia in southern China

To evaluate the impact of thalassemia carrier status on the response to controlled ovarian stimulation (COS) and outcome of intracytoplasmic sperm injection (ICSI). Seventy couples that both carried a mutation attributed to thalassemia (PGD group) and 57 couples in which only the father was a thalassemia carrier (CON group) were enrolled. All female subjects received long protocol GnRH agonist stimulation and received equivalent doses of recombinant follicle-stimulating hormone and the number of retrieved oocytes and utilisable embryos did not differ significantly. The endometrial thickness at human chorionic gonadotropin (hCG) administration day and the number of transferable embryos was lower in the PGD groups. However, pregnancy outcomes, including the clinical pregnancy rate and ongoing pregnancy rate, did not differ significantly between the two groups per cycle. Ovarian response to COS is not impaired by maternal thalassemia carrier status and embryo biopsy did not impair preimplantation embryo development or pregnancy outcomes.

A randomized, single-blind, parallel-controlled and multicentre study: compare the efficacy and safety of domestic and imported human recombinant FSH in WHO group Ⅱ anovulatory infertility

To evaluate the efficacy and safety of domestic human recombinant FSH(rhFSH)in women with anovulation of WHO group Ⅱ. A randomized, blind, parallel-controlled, non-inferiority and multicenter study was performed. A total of 534 admitted to 13 hospitals from May 2008 to August 2009. There were 531 women with ovulatory disorder was included in the statistical analysis, were randomly divided into test group(domestic rhFSH, n=352)and control group(imported rhFSH, n=179). Percentage of cycle with mature follicle, ovulation rate, clinical pregnancy rate, multiple pregnancy rate, ovarian hyperstimulation syndrome(OHSS)and adverse events were observed. No statistical significant differences(P>0.05)were observed between the two groups in terms of the efficiency on mature follicle[91.8%(323/352)versus 88.8%(159/179)], ovulation rate[91.3%(295/323)verus 90.6%(144/159)], clinical pregnancy rate[19.2%(62/323)verus 18.2%(29/159)], the number of the follicles<14 mm, the level of serum LH and progesterone, the thickness of endometrium on the day of hCG administration. The number of follicle≥18 mm and 14 mm≤follicle<18 mm and the level of serum estradiol on the day of hCG in the test group were significantly higher than those in the control group(P<0.05). The number of days of rhFSH administration in the test group was significantly less than that in the control group[(9.8±2.2)versus(11.4± 0.6)days, P<0.05], the dosage of rhFSH was significantly lower than that in the control group[(879 ± 419)versus(1 043±663)U, P<0.05]. The multiple pregnancy rate in the test group was significantly higher than that in the control group[21%(13/62)versu 10%(3/29), P<0.05]. The incidence of OHSS and adverse events were similar between the two groups(P>0.05), and no other adverse events were observed in test group during treatment. Ovarian stimulation with domestic rhFSH is effective, safe and economical in women with anovulation of WHO group Ⅱ.

Basal follicle stimulating hormone and leptin on the day of hCG administration predict successful fertilization in &lt;em&gt;in vitro&lt;/em&gt; fertilization

Background: Successful pregnancy in in vitro fertilization (IVF) program depends on multiple factors. This study aimed to determine whether age, body mass index (BMI), basal follicle stimulating hormone (FSH), estradiol, and leptin on the day of trigger ovulation with human chorionic gonadotropin (hCG) might be used as predictor for successful oocyte fertilization in in vitro fertilization (IVF) program.Methods: This is a cross sectional study conducted in Yasmin Fertility Clinic, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Forty participating patients underwent IVF program, excluding smokers, patients with diabetic, morbid obesity, and severe oligospermia or azoospermia. Age, BMI, basal FSH, estradiol, leptin on the day of hCG administration, oocyte count on oocyte retrieval, the number of mature oocyte, and fertility rate were analyzed using bivariate and multivariate analysis to determine which eligible factors play role in predicting the successful of fertilization.Results: Significant correlation was found between basal FSH level and serum leptin/oocyte ratio on the day of hCG administration with successful fertilization. We found probability formula as follows: 1/(1+exp –(6.2 - 0.4(leptin serum/oocyte ratio) - 0.8(basal FSH)), with 77.8% sensitivity, 77.8% specificity, and AUC levels of 85.6% indicating strong predictability. Probability of successful fertilization related to basal FSH level of 5.90 mIU/mL and leptin serum/oocyte ratio of 3.98.Conclusion: The formula consisting of basal FSH and leptin serum/oocyte ratio on the day of trigger ovulation was capable in predicting the probability of successful fertilization in IVF procedure.

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol.

Study QuestionWhat is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels?Summary AnswerThe optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.What Is Known AlreadyIn comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1–2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol.Study Design, Size, DurationFrom the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses.Participants/Materials, Setting, MethodsThe threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a combination of both, were determined.Main Results and the Role of ChanceThe optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS.Limitations, Reasons for CautionThis was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins.Wider Implications of the FindingsFor patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy.Trial RegistrationClinicalTrials.gov NCT00702845NCT00696800NCT00696878

Comparative study of highly purified HMG versus recombinant FSH + recombinant LH in ovulation induction for intrauterine insemination: A randomized controlled trial

IntroductionThis study sought to compare the ovarian response and follicular dynamics after stimulation with HP-hMG vs. rFSH+rLH in ovulation induction treatment. We hypothesized that the administration of 75IU of HP-hMG should be similar to 75IU of rFSH+75IU of rLH in terms of ovarian response. Material and methodProspective, randomized, open-label study was conducted in the Instituto Valenciano de Infertilidad (IVI). It included 75 patients<39 years undergoing IUI, of whom 66 were randomly assigned to one of the following groups: (1) 75IU/day rFSH+75IU/day rLH; or (2) 75IU/day HP-hMG. The objective was to compare follicular dynamics and the sample size was calculated to detect a difference in the increase in serum estradiol (E2) of 75pg/mL between days 1 and 6 of stimulation. ResultsNo differences were observed in terms of serum E2 increase, follicles recruited on day 6, serum E2 the day of hCG administration and days of stimulation. Rates of cancellation, pregnancy, pregnancy loss and clinical pregnancy between the two groups were similar. Although no statistically significant differences in the distribution of mature, medium-sized and small follicles were observed on the day of hCG administration, the number of medium-sized follicles tended to be lower in the group receiving HP-hMG. DiscussionStimulation with rFSH+rLH or HP-hMG offers similar results in terms of ovarian response, demonstrating that bioactivity is comparable between the two treatments when administered in the same ratio. The additional advantage of HP-hMG is the lower proportion of medium-sized follicles, which could be responsible for an increased risk of OHSS and multiple gestations. Administration of HP-hMG can be a valid and safe option for the induction of ovulation in IUI.

What is the best treatment for women with polycystic ovarian syndrome and high LH/FSH ratio? A comparison among in vitro fertilization with GnRH agonist, GnRH antagonist and in vitro maturation.

To evaluate whether high LH/FSH ratio has a clinical impact on patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) with GnRH-agonist/antagonist protocols or in vitro maturation (IVM) treatments. We retrospectively reviewed all PCOS patients with day 3 LH/FSH ratio ≥1.5 who underwent IVF or IVM. The main outcomes measures were embryo quality and pregnancy rate. A total of 75 cycles were included. Among these, 44 patients underwent long agonist protocol, 16 antagonist protocol and 15 IVM. Age, basal LH and FSH levels, as well as duration of infertility were comparable for all groups. The LH level on the day of hCG administration was significantly lower in the antagonist group (0.9IU/ml) compared to the long agonist group (1.4IU/ml, p=0.01). There was no difference in pregnancy rates among the groups: 27.2% in the long agonist group, 37.5% in the antagonist group and 26.6% among the IVM patients. High LH/FSH ratio had no adverse effect on pregnancy rates in all three treatment modes.

The effect of endometrial thickness on the day of hCG administration on pregnancy outcome in the first fresh IVF/ICSI cycle

The aim of this study was to investigate the effect of endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. A retrospective study was conducted on the clinical data of 756 patients in their first fresh IVF/ICSI cycle at the Wuxi Maternity and Child Health Hospital. Compared with the pregnancy failure group, the clinical pregnancy group had more transferable embryos and good-quality embryos and had a thicker endometrium (p < 0.05). The endometrial pattern was not significantly different between the two groups. EMT was found to be an independent prognostic factor for clinical pregnancy (adjusted OR = 1.25, 95% CI: 1.15–1.36, p < 0.01). Seven hundred and fifty-six cycles were categorized into three groups upon EMT on the hCG day: group 1 (EMT < 8 mm), 2 (EMT 8–14 mm) and 3 (EMT > 14 mm). Group1 had significantly lower clinical pregnancy, embryo implantation and live birth rates compared with group 2 and 3 (p < 0.01), while there was no significant difference in either spontaneous abortion or multiple-birth rate among these three groups. It was concluded that EMT on the hCG day was associated with pregnancy outcome in the first fresh IVF/ICSI cycle. A higher clinical pregnancy rate could be achieved when EMT ≥ 8 mm, and no adverse pregnancy outcome was observed when EMT > 14 mm.

Empty Follicle Syndrome-Oocyte Could be Retrieved in Consecutive Cycle

Empty follicle syndrome (EFS), reported in patients undergoing IVF treatment with no oocytes is obtained after ovarian stimulation. The publications regarding EFS are limited and there is no consensus of its etiology. The aim of our study was to characterize the cycles with EFS and evaluate the possible reasons for its occurrence. The incidence of EFS in our cohort was 4.9% per cycle or 6.2% per patient. On the day of hCG administration the mean E2 and P4 levels were 1856 ± 1154 pg/ml and 0.98 ± 0.87 ng/ml, respectively, in our patients (control group) as compared to 610 ± 178 pg/ml (p<0.05) and 0.7 ± 0.4 ng/ml, respectively, for cycles with EFS. The mean follicle number per patient in the control group was 6.4 ± 4.1; however, the mean follicle number in patients with no oocytes in the follicular fluid (FF) was 2.5 ± 2.2. In the EFS group the measured level of AMH was 0.5 ± 0.3. Double dose of rec-hCG in consecutive cycles of the EFS group, using a similar COH protocol or changed COH regimen with regular dose of rec-hCG, resulted in oocyte aspiration in most cases with previous EFS cycles. From 150 oocytes retrieved in the 34 successful consecutive cycles of the EFS group, 37% of oocytes were immature (MI stage) and 63% mature (M II) oocytes, the same percentage as was found in our control sub-group (women over 35 years old). We suggest that EFS may be the result of a delayed maturation of oocyte-cumulus complexes. The cases of EFS are sporadic and, in our opinion, can’t be defined as a syndrome. We suggest the use of a different name for EFS, such as “Failure of Oocyte Retrieval” (FOR).

Hormonal responses and clinical outcome are the same with three doses of gonadotropin-releasing hormone agonist used in the short stimulation protocol.

The aim of this study was to compare 3 different doses of GnRH-a in a short protocol on ICSI outcome. 91 ovulatory patients were randomly assigned to three groups; group A (N=34), group B (N=34) and group C (N=23). All started treatment with urinary gonadotropins, 2 ampoules per day and GnRH-a (Triptorelin) on the first day of the menstrual period and continued till the day of (hCG) administration. The daily dose of Triptorelin was 0.1 mg, 50 µg, and 25 µg in groups A, B and C respectively. Stimulation requirements, days of stimulation and total ampoules of gonadotropins did not differ between the three groups. The mean number of follicles aspirated and the mean number of Metaphase 2 oocytes retrieved were similar in the three groups. Fertilization and cleavage rates were similar in the three groups. The mean number of embryos available for transfer was 6.4±0.5, 9.4±0.5 and 7±0.7 in groups A, B and C, with a significant difference only between groups A and B. Pregnancy rates per cycle were 35.3%, 35.3% and 34.8 % for groups A, B and C, respectively with no significant difference. Early and late hormonal changes, stimulation requirements and final outcome were similar with the different doses of the agonist. Other factors should be considered, most importantly: treatment cost and side effects.

The Impact of Endometrial Thickness on the Day of Human Chorionic Gonadotrophin (hCG) Administration on Ongoing Pregnancy Rate in Patients with Different Ovarian Response.

In order to explore the impact of endometrial thickness on hCG administration day on ongoing pregnancy rate (OPR) in IVF-ET cycles, we retrospectively analyzed data from 10,406 patients undergoing their first IVF cycles with standard gonadotropin releasing hormone analogue (GnRH-a) long protocol. Firstly, patients were divided into poor (≤ 5 oocytes), medium (6–14 oocytes), and high (≥ 15 oocytes) ovarian responders based on the number of oocytes retrieved. In each group, patients were sub-divided into three groups according to the endometrial thickness on the day of hCG administration: Group A, thin endometrial thickness (≤ 7 mm); Group B, medium endometrial thickness (8–13 mm); Group C, thick endometrial thickness (≥ 14 mm). (1) For poor responders, OPRs were significantly different in the three endometrial thickness groups (28.57%, 44.25%, and 51.34%; P = 0.008). The association between thin endometrial thickness and OPR was significant after controlling for age, number of embryos transferred by multivariate logistic regression analysis (adjusted OR: 0.408; 95% CI: 0.186–0.898; P = 0.026. Reference = thick endometrial thickness). (2) For medium responders, OPRs were 31.58%, 55.56%, and 63.01% (P = 0.000) in the three groups. Adjusted OR for thin endometrial thickness was 0.284 (95% CI: 0.182–0.444; P = 0.000). (3) For high responders, OPRs were also significantly different in the three groups (28.13%, 52.63%, and 63.18; P = 0.000). Adjusted OR for thin endometrial thickness was 0.233 (95% CI: 0.105–0.514; P = 0.000). For patients undergoing IVF with different ovarian response, a thin endometrium on the day of hCG administration adversely affects ongoing pregnancy rate.

Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? A randomized, controlled trial

To evaluate the effectiveness of the addition of growth hormone (GH) to the antagonist protocol in IVF/intracytoplasmic sperm injection cycles in poor responders. Parallel randomized, controlled, open-label trial. University hospital. A total of 141 patients (GH, n = 68; gonadotropins only, n = 73) were enrolled. Twenty-five patients had their cycles cancelled. Analysis was performed per cycle start as well as per ET. Patients received the antagonist protocol with or without GH supplementation. Mean number of cumulus complexes, metaphase II oocytes retrieved and fertilized, chemical and clinical pregnancy rates, early miscarriage rate, ongoing pregnancy and live birth rates. The addition of GH significantly lowered duration of hMG treatment, duration of GnRH antagonist treatment, and dose of gonadotropin. It significantly increased mean E2 levels on the day of hCG administration, number of collected oocytes (7.58 ± 1.40 vs. 4.90 ± 1.78 [mean ± SD]), number of metaphase II oocytes (4.53 ± 1.29 vs. 2.53 ± 1.18), number of fertilized oocytes (4.04 ± 0.96 vs. 2.42 ± 1.03), and number of transferred embryos (2.89 ± 0.45 vs. 2.03 ± 0.81). There was no significant difference in the clinical pregnancy rate per cycle (22.1% vs. 15.1%) or live birth rate per cycle (14.7% vs. 10.9%). Growth hormone as an adjuvant treatment in IVF/intracytoplasmic sperm injection cycles for poor responders should be cautiously used with the antagonist protocol, because there is still no identified impact on pregnancy outcomes. However, evaluation of the clinical pregnancy and live birth rates in our data was limited by low statistical power. ClinicalTrials.gov Identifier: NCT02195947.

127 THYROID STIMULATING HORMONE LEVEL CHANGE DURING CONTROLLED OVARIAN STIMULATION

Women who undergo assisted reproductive technology (ART) are exposed to a supra-physiological hormonal environment, which can affect the hypothalamus-pituitary-thyroid axis. Understanding these changes can help us improve the outcomes of ART. In this study we discuss the changes of thyroid hormone levels during ovarian stimulation as part of intrauterine insemination (IUI) and compare hypothyroid and euthyroid patients. Fifty-two infertile women aged 22 to 40 who underwent induction ovulation (I/O) as part of IUI were enrolled in this study. Out of 52 patients, 13 had underlying thyroid disease receiving levothyroxine treatment, and their thyroid test results were normal (&lt;2.5) for more than 6 weeks and had taken fixed levels of levothyroxine for more than 6 weeks. The TSH levels were measured by electrochemiluminescence at 3 times: baseline TSH (before starting of I/O), the day of HCG administration, and 4 weeks after. The change of TSH levels during this period and its relationship with baseline hypothyroidism, oestradiol levels, and I/O and pregnancy outcome were studied. Mean central index, frequency percentage, the median, and dispersion of standard deviation and interquartile range (IQR) were used to describe the data. Statistical tests, including t-test and chi-square, were used to analyse the data. Mean difference and relative risk indices were used to measure the differences. There was a significant increase in TSH level at the time of hCG injection compared with basal TSH in hypothyroid patients under treatment, TSH increased from 1.61 ± 0.81 to 2.75 ± 1.86 (P = 0.045), and this increase was seen in TSH 4 weeks later from 1.61 ± 0.81 to 2.12 ± 0.87 (P = 0.026). However, there were not significant changes in thyroid hormone level during treatment in euthyroid patients. In hypothyroid patients who got pregnant, there was no significant increase in 3 TSH measurements. But for the patients with an unsuccessful cycle this increase was seen at the time of HCG injection and 4 weeks later in comparison with basal TSH, which was statistically significant: 1.55 ± 0.83 v. 2.97 ± 2.09 (P = 0.05) and 1.55 ± 0.83 v. 2.14 ± 0/99 (P = 0.039). But this change was not seen in euthyroid patients with successful and unsuccessful cycle results. The relationship between TSH level with oestradiol in both euthyroid and hypothyroid patients was not significant. There was not a significant correlation between the number of follicles bigger than 16 mm, the mean size of follicles, and endometrial thickness with TSH at the time of HCG injection in both hypothyroid and euthyroid patients. There was a negative and reverse correlation between endometrial thickness and TSH at the time of HCG injection, but it was not significantly different. (P = 0.05). In euthyroid patients who undergo I/O as part of IUI, we did not observe significant TSH level changes during I/O, but in controlled hypothyroid patients a rise in serum TSH levels was observed. The pregnancy rate between 2 euthyroid and controlled hypothyroid groups was not different.

Effect of premature serum progesterone rise on embryo transfer outcomes and the role of blastocyst culture and transfer in assisted reproductive technology cycles with premature progesterone rise

ObjectiveIn 1991, researchers reported that a modest preovulatory increase in serum progesterone levels is associated with lower pregnancy rates and higher incidence of pregnancy loss in in vitro fertilization (IVF). We wonder whether embryo transfer (ET) in assisted reproductive technology (ART) cycles in patients with premature progesterone rise (PPR) have a negative impact on the clinical pregnancy rates (CPRs) and/or live birth rates (LBRs) in our series. Consequently, will blastocyst transfer reverse the negative impact? Materials and methodsThis noninterventional, retrospective, observational tertiary center study was conducted between January 2010 and December 2012. All fresh ET cycles with serum progesterone levels measured (n = 599) on the day of hCG administration were analyzed. ResultsSera lutenizing hormone (LH), E2, and progesterone (P) were measured and analyzed. The CPRs of cycles in patients with p ≤ 1.5 ng/mL (low) versus those with p > 1.5 ng/mL (high) were 37.04% versus 41.03% [odds ratio (OR) = 1.18, 95% confidence interval (CI): 0.728–1.920; p = 0.50). The LBRs of cycles in patients with low progesterone level versus those with PPR were 30.52% versus 34.62% (OR = 1.21, 95% CI: 0.729–1.992; p = 0.47). No statistically significant association was detected. We further analyzed the outcomes according to different stages of ET and found that blastocyst (D5) ET significantly increase the LBRs as compared with cleavage stage (D2/D3) ET in the PPR group (44.44% versus 21.43%; p = 0.043). ConclusionPPR did not significantly compromise the clinical outcomes in this series. However, shifting to blastocyst transfer probably could increase the live birth in cycles with PPR.

A simplified universal approach to COH protocol for IVF: ultrashort flare GnRH-agonist/GnRH-antagonist protocol with tailored mode and timing of final follicular maturation.

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000–10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35–37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.

Is the GnRH Antagonist Protocol Effective at Preventing OHSS for Potentially High Responders Undergoing IVF/ICSI?

ObjectiveTo determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders.MethodsA total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared.ResultsThe duration of stimulation, E2 level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05).ConclusionsOur study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates.

Thyroid function and autoimmunity during ovarian stimulation for intracytoplasmic sperm injection.

The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P=0.066). In women who became pregnant (n=8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410±1.200 vs 2.014±0.950μIU mL-1, respectively; P=0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r=-0.7, P=0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant.

The effect of a high progesterone concentration before oocyte retrieval on the peri-implantation endometrium

In this single-centre, prospective cohort study, the effect of high progesterone level before oocyte retrieval on endometrial morphology and uterine natural killer cell (uKN) count in the peri-implantation period was investigated. A total of 106 women undergoing IVF treatment who did not proceed to fresh embryo transfer were included. Endometrial samples were obtained 7 days after HCG administration. Multiple regression analysis was used to identify factors affecting the results of histological staging and uNK cell count. Progesterone level on the day after HCG administration was the only significant variable associated with the results of histological staging (P = 0.004). Endometrial development in women with high progesterone level was significantly (P < 0.001) more advanced than that of women with normal progesterone; progesterone level on the day of HCG administration was the only significant variable associated with uNK cell count. The median (range) of uNK cell count of 9.6% (2.3–21.6%) in women with high progesterone was significantly (P < 0.001) higher than the median (range) of uNK cell count of 5.7% (1.4–18.7%) in women with normal progesterone. High progesterone level before oocyte retrieval was correlated with advancement in endometrial development as well as increased uNK cell count.

Frozen-thawed embryo transfer in a natural or mildly hormonally stimulated cycle in women with regular ovulatory cycles: a RCT.

Can ovarian stimulation with low dose hMG improve the implantation rate (IR) per frozen-thawed embryo transferred (FET) when compared with natural cycle in an FET programme in women with a regular ovulatory cycle? Both IR and live birth rate (LBR) per FET were similar in the group with mild ovarian stimulation and the natural cycle group. Different cycle regimens for endometrial preparation are used prior to FET: spontaneous ovulatory cycles, cycles with artificial endometrial preparation using estrogen and progesterone hormones, and cycles stimulated with gonadotrophins or clomiphene citrate. At present, it is not clear which regimen results in the highest IR or LBR. More specifically, there are no RCTs in ovulatory women comparing reproductive outcome after FET during a natural cycle and during a hormonally stimulated cycle. A total of 410 women scheduled for FET during 579 cycles (December 2003-September 2013) were enrolled in an open-label RCT to natural cycle (NC FET group, n = 291) or to a cycle hormonally stimulated with s.c. gonadotrophins (hMG FET group, 37.5-75 IU per day, n = 288). A total of 672 embryos were transferred during 434 cycles (332 embryos and 213 cycles in the NC FET group; 340 embryos and 221 cycles in the hMG FET group). Assuming a = 0.05 and 80% power, it was calculated that 219 frozen-thawed embryos were required for transfer in each group to demonstrate a difference of 10% in IR. Women were eligible according to the following inclusion criteria: regular ovulatory cycle, female age ≥21 years and ≤45 years, informed consent. FET cycles with preimplantation genetic screening were excluded. The primary outcome was IR per embryo transferred. Secondary outcomes included IR with fetal heart beat (FHB), LBR per embryo transferred and endometrial thickness on the day of hCG administration. Statistical analysis was by intention to treat and controlled for the presence of multiple measures, as eligible women could be randomized in more than one cycle. Chi-square and independent t-test were used to compare categorical and continuous variables. The relative risk (RR) was estimated using a Poisson model with log link. Hierarchical models with random intercepts for patient and cycle were considered to account for clustering of cycles within patients and of embryos within cycles. The primary outcome, IR per embryo transferred, was not statistically different between the NC FET group (41/332 (12.35%)) and in the hMG FET group (55/340 (16.18%)) (RR 1.3 (95% confidence interval (CI) 0.9-2.0), P = 0.19). Similarly, the secondary outcome, IR with FHB per embryo transferred, was 34/332 (10.24%) in the NC FET group and 48/340 (14.12%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.1), P = 0.15). The LBR per embryo transferred was 32/332 (9.64%) in the NC FET group and 45/340 (13.24%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.2), P = 0.17). Endometrial thickness was also similar in both groups [8.9 (95% CI 8.7-9.1) in the NC FET group and 8.9 (95% CI 8.7-9.1) in the hMG FET group]. The duration of the follicular phase was significantly shorter (P < 0.001) in the hMG FET group [13.7 days (95% CI 13.2-14.2)] than in the NC FET group [15.4 days (95% CI 14.8-15.9)]. Randomization of cycles instead of patients; open-label design; relatively long period of recruitment. Our observation that the IR per embryo transferred is not significantly increased after FET during natural or gonadotrophin stimulated cycle, suggests that the effect of mild hormonal stimulation with gonadotrophins is smaller than what was considered clinically relevant with respect to reproductive outcome after FET. These data suggest that endometrial receptivity is not relevantly improved, but also not impaired after hormonal stimulation with gonadotrophins. Since FET during a natural cycle is cheaper and more patient-friendly, we recommend this regimen as the treatment of choice for women with regular cycles undergoing FET. clinicaltrials.gov NCT00492934. 26 June 2007. 1 December 2003.

The effect of LH supplementation to the GnRH antagonist protocol in advanced reproductive ageing women: a prospective randomized controlled study.

Although the fundamental significance of both LH and FSH for adequate ovarian folliculogenesis and steroidogenesis has been extensively discussed, the clinical implication of recombinant (r) LH to rFSH for ovarian stimulation employing the GnRH antagonist protocol remains to be elucidated. The aim of this prospective randomized controlled study was to explore whether rLH supplementation to rFSH following GnRH antagonist has an added value to the late follicular ovarian steroidogenesis in the advanced reproductive aged women. Sixty-three consecutive infertile women above 35 years of age and/or with a previous low ovarian response admitted for IVF/ICSI treatment were prospectively randomized. Women in the study and control groups were similarly treated employing the rFSH 300 IU/day and the flexible GnRH antagonist 0·25 mg/day protocol. On the day of antagonist initiation, rLH 150 IU/day was added only to the study group and continued till the hCG day. Serum E2 level on hCG day did not significantly differ between the study and control groups, corresponding to 1268 ± 1006 and 1113 ± 669 pg/mL, respectively (P = 0·9). In the study group, the duration of GnRH antagonist administration was significantly lower than the control group corresponding to 5·0 ± 1·5 to 4·0 ± 1·5 days, respectively (P < 0·05). The total dosage of rFSH administration did not differ between the two groups. rLH supplementation to rFSH following GnRH antagonist administration employing the flexible protocol does not seem to significantly augment serum E2 level on the day of hCG administration in the advanced reproductive ageing women. This suggests that endogenous serum LH levels following GnRH antagonist initiation are sufficient for adequate late follicular ovarian steroidogenesis in this setting.

Elevated progesterone level on the day of HCG administration does not impact live birth rates following stimulation with HP-hMG and HP-FSH at a 0.5 LH/FSH ratio

The role of elevated progesterone (P4) levels on implantation success is controversial. Some studies have suggested that premature progesterone rise (PPR) (defined as peak P4 levels >1.5 ng/ml) has a detrimental effect on IVF success, while others have been unable to demonstrate a negative effect. Recent data demonstrated that using ovarian stimulation with an LH/FSH ratio in the range of 0.3-0.6 yielded the lowest chance of PPR compared with ratios > 0.6 (Warner et al).