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

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

Download Full-text

Endometrial compaction and serum progesterone measurements at the day of embryo transfer cannot predict pregnancy outcomes in frozen-thaw embryo transfer cycles

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v12i1.4050 ◽

2021 ◽

Vol 12 (1) ◽

pp. 407-415

Author(s):

Dalal M. Al Jarrah ◽

Manal Taha Al Obaidi ◽

Itlal J. AL Asadi

Keyword(s):

Pregnancy Rate ◽

Embryo Transfer ◽

Pregnancy Outcomes ◽

Endometrial Thickness ◽

Transvaginal Ultrasound ◽

P Value ◽

Ongoing Pregnancy ◽

Ongoing Pregnancy Rate ◽

Serum Progesterone ◽

The Impact

Endometrial receptivity plays a basic role in successful embryo implantation and pregnancy outcomes and can be assessed by many of non-invasive markers. Our study evaluated the impact of two of these markers specifically serum progesterone and endometrial thickness at embryo transfer day in prediction pregnancy outcomes on (60) patients attempting medicated frozen embryo transfer (FET) cycles. All patients were received sequential estrogen & progesterone medications for endometrial preparation then submitted to measurements of endometrial thickness (EMT) by transvaginal-ultrasound (TV-US) & serums progesterone (P) analysis at the embryo transfer day, thereafter day 3 verified-thawed embryos grades (A±B) were transferred. Compacted (decreased) EMT was seen in 48.3% of patients with higher pregnancy rate (PR) of 58.6%t than non-compacted EMT (no change or increased) which was seen in 51.7% of patients with (PR) of 29.0%, (P value=0.021). However ongoing pregnancy rate (Ong PR) not differed significantly between both groups (44.8% in compacted vs 25.8% in non-compacted, P value=0.053), also the means of serum P not differed between pregnant and non-pregnant patients (P value=0.374). ROC curves for Ong PR prediction in relations to endometrial compaction & serum progesterone at embryo transfer day were poor (AUC= 0.630, & AUC=0.576, respectively). This study suggested that endometrial compaction or serum P levels measurements at embryo transfer day were poor predictors for ongoing pregnancy where any kind of EMT changes (decreased or not) seen after P administration not significantly affect pregnancy outcomes in frozen-thaw cycles of cleavage stage embryos transfer.

Download Full-text

P–151 Correlation between the first euploid frozen-thawed blastocyst embryo transfer (FBT) and the subsequent euploid FBT outcome originating from the same cohort of oocytes

Human Reproduction ◽

10.1093/humrep/deab130.150 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

R Abalı ◽

F K Boynukalın ◽

M Gültomruk ◽

Z Yarkiner ◽

M Bahçeci

Keyword(s):

Regression Analysis ◽

Pregnancy Rate ◽

Pregnancy Outcome ◽

Embryo Transfer ◽

Live Birth ◽

Endometrial Thickness ◽

Clinical Pregnancy ◽

Clinical Pregnancy Rate ◽

Ongoing Pregnancy ◽

Ongoing Pregnancy Rate

Abstract Study question Does the outcome of the first euploid frozen-thawed blastocyst embryo transfer affect the subsequent euploid FBT originating from the same cohort of oocytes? Summary answer The clinical pregnancy rate and ongoing pregnancy rate of the subsequent FBT are higher if a clinical pregnancy was attained in the first euploid FBT. What is known already Numerous factors including patient, cycle and embryological characteristics affect the outcome of an IVF treatment cycle. There is no data available whether the outcome of euploid FBT has an impact on the outcome of the subsequent euploid FBT of embryos originating from the same cohort of retrieved oocytes. Study design, size, duration The study enrolled cycles preimplantation genetic test for aneuploidy (PGT-A) performed between January 2016 and July 2019 at the Bahceci Fulya IVF Center. A total of 1051 patients with single euploid FBT were evaluated and resulted live birth (n = 589, live birth rate (LBR): 56%(589/1051)), miscarriage (n = 100, miscarriage rate (MR): 14.5% (100/689)) and no clinical pregnancy (n = 362, 34,4%, (362/1051)). 159 FBT after the first single euploid FBT originating from the same cohort of oocytes were analyzed. Participants/materials, setting, methods Second euploid FBT cycle after first FBT with a clinical pregnancy were compared to frozen-thawed cycles after a without a pregnancy. Logistic regression analysis was utilized to adjust for potential confounders including female age, body mass index, embryo quality, day of embryo frozen, number previous failed attempt, number of previous miscarriage, endometrial thickness, outcome of the first euploid FBT. Main results and the role of chance The pregnancy outcome from the first euploid FBT in the study group was resulted live birth (25.1%, (40/159)), miscarriage (15.7%, (25/159)) and no clinical pregnancy (59.1%, (94/159). The pregnancy outcome of the subsequent euploid embryo transfer from the same oocyte cohort was clinical pregnancy rate (CPR): (67.3%, (107/159) ongoing pregnancy rate (OPR) (52.2% (83/159) and MR (22.4%, (24/107)). The CPR in the subsequent euploid FBT was 80% (52/65) among patients who achieved a clinical pregnancy in the first euploid FBT and 58.5% (55/94) of those who did not (p = 0.0045). The OPR in the subsequent euploid FBT was 64.6% (42/65) among patients who achieved a clinical pregnancy in first euploid FBT and 43.6% (41/94) of those who did not (p = 0.009). On a multivariate regression analysis, clinical pregnancy in the first euploid FBT was a significant independent predictor for a pregnancy in the subsequent FBT transfer (p = 0.003). Limitations, reasons for caution The limitation of the study is in the retrospective nature of the study. As the PGT-A strategy significantly decreases number of transferable embryos, the sample size of the study is limited. Wider implications of the findings: Identifying predictive factors for the success of euploid FBT is important. These can help physicians while counseling patients regarding the outcome of the previous euploid FBT. Trial registration number NA

Download Full-text

The correlation between endometrial thickness and pregnancy outcomes in fresh ART cycles with different age groups: a retrospective study

Middle East Fertility Society Journal ◽

10.1186/s43043-019-0013-y ◽

2019 ◽

Vol 24 (1) ◽

Author(s):

Maryam Eftekhar ◽

Sara Zare Mehrjardi ◽

Behnaz Molaei ◽

Fatemeh Taheri ◽

Esmat Mangoli

Keyword(s):

Pregnancy Rate ◽

Pregnancy Outcomes ◽

Endometrial Thickness ◽

Age Groups ◽

Invasive Technique ◽

Main Role ◽

Ongoing Pregnancy Rate ◽

Vitro Fertilization ◽

The Impact

Abstract Background In assisted reproductive technology (ART) cycles in addition to embryo quality, the receptivity of the endometrium plays the main role in clinical outcomes. Endometrial receptivity is necessary to implantation of an embryo, and ultrasound has been established as an appreciated, simple, and non-invasive technique in the evaluation of the endometrial preparation before embryo transfer in fresh in vitro fertilization (IVF) cycles. Debate on the predictive value measuring endometrial thickness before administering human chorionic gonadotropin (HCG) for ovulation triggering in ART is ongoing. In order to explore the impact of endometrial thickness on triggering day on ongoing pregnancy rate (OPR) in ART cycles, we retrospectively analyzed data from 1000 patients undergoing IVF/ICSI cycles. Results The data showed pregnancy rate was increased in the endometrial thickness of 8 mm to 11 mm then decreased, and in endometrial thickness (Ent) > 14 mm, pregnancy rate was zero. There were significant differences in endometrial thickness and pregnancy outcomes between different age groups. The pregnancy rate was higher (32%) in 23–30 years old women, and the range of Ent in this group was 6–12 mm. Also, the data showed a positive correlation between Ent with AMH and estradiol levels and the number of COC and MII oocytes and a negative correlation between female age with Ent. Conclusion The result showed that Ent on hCG administration day is associated with pregnancy outcomes in fresh IVF/ICSI cycles with different age groups, although some of the clinical parameters may have an effect on Ent. Large studies are needed to make a definitive conclusion.

Download Full-text

Ovarian response to the human chorionic gonadotrophin stimulation test in normal ovulatory women: the impact of regressing corpus luteum

Fertility and Sterility ◽

10.1016/j.fertnstert.2006.08.114 ◽

2007 ◽

Vol 87 (5) ◽

pp. 1122-1130 ◽

Cited By ~ 9

Author(s):

Ilkka Y. Järvelä ◽

Maarit Niinimäki ◽

Hannu Martikainen ◽

Aimo Ruokonen ◽

Juha S. Tapanainen

Keyword(s):

Corpus Luteum ◽

Ovarian Response ◽

Chorionic Gonadotrophin ◽

Human Chorionic Gonadotrophin ◽

Stimulation Test ◽

The Impact

Download Full-text

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

10.21203/rs.3.rs-76107/v1 ◽

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.

Download Full-text

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 ◽

10.1136/bmjopen-2020-047974 ◽

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.

Download Full-text