Endometrial quality at the end of controlled ovarian stimulation predicts ongoing pregnancy rate after transfer of a single expanded or hatching/hatched blastocyst on day 5 in a fresh cycle

2012 ◽  
Vol 98 (3) ◽  
pp. S225
Author(s):  
R.A. Pierson ◽  
M. Mrázek ◽  
W. Kuzcynski ◽  
B.M. Klein ◽  
J.-C. Arce
Keyword(s):  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Controlled Ovarian Stimulation ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate

O-109 A first dose-response trial investigating the effects of adding choriogonadotropin beta to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Fernandez Sanchez ◽  
H Višnová ◽  
C Blockeel ◽  
A Pinborg ◽  
Y Khalaf ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Cell Line ◽  
Gnrh Agonist ◽  
Ovarian Stimulation ◽  
Randomised Trial ◽  
Chinese Hamster ◽  
Ongoing Pregnancy ◽  
Cho Cell ◽  
Ongoing Pregnancy Rate ◽  
Cho Cell Line

Abstract Study question Does addition of choriogonadotropin beta (CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? Summary answer At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and decreased the number of oocytes and blastocysts. What is known already CG beta is a new recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6â) with a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell-line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the area under the curve (AUC) and the peak serum concentration (Cmax) increased dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than rhCG derived from a CHO cell line. Study design, size, duration Placebo-controlled, double-blind, randomised trial (RAINBOW) to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing COS in a long GnRH agonist protocol. The primary endpoint was the number of good-quality blastocysts (grade 3 BB or higher, Gardner and Schoolcraft, 1999). Subjects were randomised to receive either placebo or 1, 2, 4, 8, or 12 µg CG beta added to the daily individualised follitropin delta dose during COS. Participants/materials, setting, methods In total 619 women (30-42 years) with AMH levels between 5 and 35 pmol/L were randomized in equal proportions to the six treatment groups. All subjects were treated with an individualised dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached Main results and the role of chance The incidence of cycle cancellation (range 0%-2.9%), total follitropin delta dose (mean 112 µg) and duration of stimulation (mean 10 days) were similar across the groups. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of goodquality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 µg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was high i.e. 43% per started cycle vs 28-39% in CG beta groups and 49% per transfer vs 38-50% in the CG beta groups. In line with the number of collected oocytes, the OHSS incidence was overall lower following follitropin delta with CG beta than following follitropin delta only treatment. Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. Limitations, reasons for caution The effect of the unique glycosylation of CG beta and the associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate potentially lower doses of CG beta for this and/or different indications. Wider implications of the findings The high ongoing pregnancy rate in the follitropin delta group supports the use of individualised follitropin delta dosing in a long GnRH agonist protocol. The differential potency of CG beta may have impaired the growth of intermediate follicles with the investigated doses without affecting the ongoing pregnancy rates per transfer. Trial registration number NCT03564509

scholarly journals Endometrial thickness as a biomarker for ongoing pregnancy in IUI for unexplained subfertility: a secondary analysis

2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
N A Danhof ◽  
R van Eekelen ◽  
S Repping ◽  
B W J Mol ◽  
F van der Veen ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Conflicts Of Interest ◽  
Endometrial Thickness ◽  
Secondary Analysis ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Cycle Number ◽  
The Impact

Abstract STUDY QUESTION What is, in couples with unexplained subfertility undergoing IUI, the impact of gonadotrophins compared to clomiphene citrate (CC) on endometrial thickness (EMT) in relation to ongoing pregnancy? SUMMARY ANSWER In women with unexplained subfertility undergoing IUI with ovarian stimulation, gonadotrophins lead to a thicker endometrium compared to CC, but this does not affect ongoing pregnancy rates. WHAT IS KNOWN ALREADY A systematic review and meta-analysis among couples with unexplained subfertility undergoing IUI with ovarian stimulation showed that women who conceived had, on average, a thicker endometrium than women who did not conceive, but this evidence is not robust due to a high level of heterogeneity. There was insufficient data to draw any conclusions on EMT and the effect on pregnancy outcomes. STUDY DESIGN, SIZE, DURATION We performed a secondary analysis of a multicentre randomized controlled superiority trial in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria. In total, 738 couples recruited between July 2013 and March 2016 were allocated to ovarian stimulation with gonadotrophins (n = 369) or with CC (n = 369) for a maximum of four IUI cycles. According to local protocol, recombinant FSH, urinary FSH or hMG was used. Natural conceptions and cancelled cycles were removed from this secondary analysis, as they do not provide any information on pregnancy in relation to stimulation after IUI. Ongoing pregnancy was defined as a positive heartbeat at or beyond 12 weeks of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS We first determined the difference in EMT between women randomized to gonadotrophins (75 IU) and CC (100 mg) over all cycles using a linear mixed model. We then investigated the association between EMT and ongoing pregnancy after IUI using a logistic regression model, adjusted for the allocated drug, number of dominant follicles, female age, BMI, duration of subfertility, primary or secondary subfertility, referral status, smoking status, cycle number and total motile sperm count. To conclude, we investigated the association between EMT and ongoing pregnancy by logistic regression separately in women allocated to gonadotrophins and in women allocated to CC. MAIN RESULTS AND THE ROLE OF CHANCE A total of 666 couples underwent 1968 IUI cycles. Of these, 330 couples were allocated to gonadotrophins, of which 85 conceived leading to ongoing pregnancy (rate per cycle 8.9%) and 336 couples were allocated to CC, of which 71 conceived leading to ongoing pregnancy (rate per cycle 7.0%) (relative risk (RR) 1.22, 95% CI 0.92 to 1.61). The mean EMT was 8.9 mm (SD 2.1) in women treated with gonadotrophins and 7.5 mm (SD 2.1) in women treated with CC (adjusted mean difference 1.4 mm; 95% CI: 1.1–1.7). The overall mean EMT was 8.4 mm (SD 2.2) in women that conceived leading to ongoing pregnancy and 8.2 mm (SD 2.2) in women that did not conceive (adjusted odds ratio (OR): 1.03 per 1 mm increase, 95% CI 0.95–1.12). There was no association between EMT and ongoing pregnancy in women treated with gonadotrophins or CC (OR: 1.01 per 1 mm increase, 95% CI 0.90–1.13, and 1.10 per 1 mm increase, 95% CI 0.99–1.23, respectively). LIMITATIONS, REASON FOR CAUTION Since this is a secondary analysis, the data should be interpreted prudently as secondary analyses are prone to false-positive findings or could be underpowered to show associations that the study is not primarily set up for. WIDER IMPLICATIONS OF THE FINDINGS In women with unexplained subfertility and treated with IUI, gonadotrophins lead to a significantly thicker endometrium compared to CC, but there was no evidence of a consistent association between EMT in women treated with gonadotrophins or CC and the ongoing pregnancy rate. A relatively thin endometrium after CC is therefore not a valid reason to prefer gonadotrophins as the stimulation agent in IUI for unexplained subfertility. STUDY FUNDING/COMPETING INTEREST(S) The initial trial was funded by the Netherlands Organization for Health Research and Development (ZonMw) (Health Care Efficiency Research; project number: 80-83600-98-10 192). The EudraCT number for this trial was 2013-001034-18. Prof. Dr B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for Merck, ObsEva and Guerbet. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NTR 4057

scholarly journals Effect of Serum Progesterone (P4) Level at the Day of Human Chorionic Gonadotropin (HCG) Administration on the Outcome of Intracytoplasmic Sperm Injection and Fresh Embryo Transfer

2020 ◽  
pp. 45-57
Author(s):  
Yasmine El- Masry ◽  
Ashraf Elmohamdy Gharib ◽  
Manal Moustafa Abd Allah
Keyword(s):  
Embryo Transfer ◽  
Ovarian Stimulation ◽  
Endometrial Thickness ◽  
Controlled Ovarian Stimulation ◽  
Ongoing Pregnancy ◽  
Fresh Embryo Transfer ◽  
Ongoing Pregnancy Rate ◽  
Luteal Support ◽  
Embryo Number

Our aim was to investigate the effect of different progesterone (P4) at day of triggering HCG on the outcomes of ICSI with fresh embryo transfer in cases who underwent controlled ovarian stimulation (COS). Pituitary desensitization done either with long agonist or antagonist pituitary desensitization protocols, then analyzing the effect of serum P4-hCG level on ICSI-fresh embryos transfer outcome including; number and quality of retrieved oocytes (OR), embryo number (ER) & quality and ongoing pregnancy outcomes. The cases are which continued their pregnancy till 12 weeks, aborted cases, ectopic pregnancy & cancelled cases (for different reasons). Materials and Methods: This prospective cohort study was carried on 120 cases who underwent ICSI cycles for different causes and types of infertility. Controlled ovarian stimulation (COS) protocol and pituitary down-regulation either by; GnRH long agonist /antagonist protocols then, fertilization, embryo grading, embryo transfer and hormonal luteal support was done. Blood samples were taken on the day of hCG administration to measure P4 in all cases. All patients who got pregnant and continue till 12 weeks, they were categorized into 3 subgroups as regard serum P4 level: Group A: (P4< 0.5 ng/ml), Group B: (P4=O.5-I.5 ng/ml) & Group C: (P4 >I.5 ng/ml) and correlated with their ICSI outcome. The outcomes of ICSI-ET cycles in those cases were compared with 3 groups of P4 levels in the controlled ovarian stimulation with two protocols. Results: P4 level had insignificant relation with number and quality of retrieved oocytes, fertilized embryo number and quality and endometrial thickness regardless the protocol of COS. The low and high levels of P4 both, had a detrimental effect on CPR, meanwhile, with no harmful impact on the ongoing pregnancy rate was noticed, regardless the protocol of ovarian stimulation. P4-hCG isn’t considered to be the only predictive measure of ICSI outcome. Highest CRP was noticed in cases with P4 level (0.5-I.5 ng/ mI) regardless the type of protocol used.

scholarly journals A Luteinizing Hormone-based Protocol Versus Traditional Flexible Gonadotropin-Releasing Hormone Antagonist Protocol in Women with Normal Ovarian Response: Study Protocol for a non-Inferiority Trial

2021 ◽  
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu
Keyword(s):  
Luteinizing Hormone ◽  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Gonadotropin Releasing Hormone ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

Abstract BackgroundUse of gonadotropin-releasing hormone (GnRH) antagonists during the late follicular phase can prevent premature luteinizing hormone (LH) surge. Many patients demonstrate an insufficient endogenous LH concentration during ovarian stimulation. Previous studies have demonstrated that ultra-low LH concentration influences pregnancy outcomes. However, affected patients cannot be distinguished prior to ovarian stimulation using baseline characteristics alone. With traditional fixed or flexible GnRH antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomized clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response. MethodsThis study was a multicenter, parallel, prospective, randomized, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with a LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate, and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 372.DiscussionThis is the first randomized controlled trial to compare the efficacy of a LH-based treatment regimen with a traditional flexible GnRH antagonist protocol during ovarian stimulation. We hypothesized no significant difference in cumulative ongoing pregnancy rate per cycle between the two protocols. Moreover, patients with insufficient endogenous LH during ovarian stimulation may benefit from LH-based GnRH antagonist protocols. The results will provide new information on when to introduce antagonists and the appropriate dosage of antagonist.Trial registration: ClinicalTrials.gov, ChiCTR1800018077. Registered on 29 August, 2018.

scholarly journals Luteinising hormone-based protocol versus traditional flexible gonadotropin-releasing hormone antagonist protocol in women with normal ovarian response: study protocol for a non-inferiority trial

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e047974
Author(s):  
Ya-su Lv ◽  
Yuan Li ◽  
Shan Liu
Keyword(s):  
Pregnancy Rate ◽  
Ovarian Stimulation ◽  
Luteinising Hormone ◽  
Gnrh Antagonist ◽  
Ovarian Response ◽  
Gonadotropin Releasing Hormone ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Gnrh Antagonist Protocol ◽  
Antagonist Protocol

IntroductionMany patients demonstrate an insufficient endogenous luteinising hormone (LH) concentration during ovarian stimulation. With traditional fixed or flexible gonadotropin-releasing hormone (GnRH) antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomised clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response.Methods and analysisThis study was a multicentre, parallel, prospective, randomised, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with an LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% drop-out rate, the total number of patients required was 372.Ethics and disseminationThis trial has been approved by the Institutional Ethical Committee of Beijing Chao-Yang hospital. All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals.Trial registration numberChiCTR1800018077.

scholarly journals CC-Human Menopausal Gonadotropin Combined with Growth Hormone in Mini-stimulation Protocol could Improve Clinical Outcome in Poor Ovarian Responders

2016 ◽  
Author(s):  
Arie A Polim ◽  
Ivan R Sini ◽  
Indra NC Anwar ◽  
Aryando Pradana ◽  
Kurniawati Kurniawati ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pregnancy Rate ◽  
Group Versus ◽  
Poor Responders ◽  
Human Menopausal Gonadotropin ◽  
Ongoing Pregnancy ◽  
Stimulation Protocol ◽  
Ongoing Pregnancy Rate ◽  
Significant Difference ◽  
Poor Ovarian Responders

Objective: To investigate the role of CC-highly purified Human Menopausal Gonadotropin (hpHMG) and Growth Hormone (GH) in mini-stimulation protocol to improve outcome in poor ovarian responders (POR). Method: All patients were given clomiphene citrate 150 mg from day 3 to day 7 of menstrual cycle followed by 150 IU hpHMG daily from day 8 until ovulation trigger. Two groups were observed where one group received GH and the other arm did not. In the GH group, 8 IU of GH were given from day 1 of stimulation until stimulation was stopped. GnRH antagonist was used to suppress ovulation. Result: Among 51 eligible women, 29 patients with GH and 22 patients without GH, no difference was observed in the number of oocytes retrieved (2.21 versus 2.64) and the number of embryos transferred (1.24 versus 1.68) in the GH group versus the group without GH, respectively. Total clinical pregnancy rate was 17.6%. No significant difference in pregnancy and ongoing pregnancy rate in both groups (17.2% versus 18.2%) and (13.8% versus 13.6%), respectively. In patients older than 40 years old, GH showed a 4-fold likelihood in producing top quality embryos (44.8% vs 13.6%, OR=3.6, p=0.05). Conclusion: CC-HMG regimen in mini-stimulation protocol is an effective option in poor responders. Additional GH in ministimulation program provided a higher number of top quality embryos in women older than 40 years old, although there were no difference in clinical or ongoing pregnancy rate. Keywords: CC-HMG, growth hormone, IVF, mini-stimulation protocol, poor ovarian responders

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