Early Luteal Hormones and IVF Outcomes After hCG Triggering

Reproductive Outcome of IVF Treatment in Relation to the Early Luteal Phase Trajectory of Progesterone and Other Corpus Luteum Related Hormones

It has recently been demonstrated that a bolus trigger of hCG induces various unphysiological conditions in the early luteal phase that may negatively affect an IVF treatment cycle's reproductive outcome. The bolus trigger of hCG differ from the natural cycle in mainly three different ways: 1) The timing of the initiation of hCG and progesterone rise is much faster after an hCG trigger than in the natural menstrual cycle 2) the maximal concentrations of hCG and progesterone considerably exceed those naturally observed 3) The timing of the peak progesterone concentration following an hCG trigger is advanced several days compared to the natural cycle. These characteristics may affect the reproductive outcome in treatment cycles but are not explored. The aim of this study is to monitor whether specific trajectories of important luteal phase hormones may predict the chances of conception?

Study Overview

• Status: Completed
• Conditions: Luteal Phase; in Vitro Fertilisation
• Intervention / Treatment: Other: Hormonal levels

Detailed Description

The early luteal phase after ovarian stimulation and final oocyte maturation using a bolus trigger of hCG is an area that has not received the same attention as regimes and protocols for ovarian stimulation during the follicular phase. The hCG trigger has been considered the golden standard since the beginning of the IVF era almost four decades ago. The hCG trigger serves two main functions: 1) it induces oocytes to advance meiosis to the metaphase of the second meiotic division ready for fertilization and further development, 2) secures stimulation of the corpora lutea to secrete progesterone (P4) during the early luteal phase due to its relatively long half-life. However, recent studies have suggested that each of these two functions may be optimized on their own and that better alternatives to the hCG trigger may be developed including a more physiological trigger for final maturation of follicles and individualized luteal phase support. However, only recently has the early luteal phase after IVF treatment using an hCG bolus trigger been described in studies involving more than just a few patients. These studies suggested that the unphysiological effects of the hCG trigger may be divided into three different categories: 1) The timing of the initiation of hCG and progesterone rise is much faster after an hCG trigger than in the natural menstrual cycle 2) the maximal concentrations of hCG and progesterone considerably exceed those naturally observed 3) The timing of the peak progesterone concentration following an hCG trigger is advanced several days compared to the natural cycle. How each of these effects influences pregnancy outcome in treatment cycles are currently unknown. Further, does characteristics shortly after administration of the hCG trigger for final oocyte maturation subsequently affect the reproductive outcome, and does this provide an opportunity for correcting or improving the luteal phase support given, with the improvement of clinical pregnancy rate as a result is also unknown. The aim of this study is to evaluate the trajectories of four hormones important for corpora lutea function (i.e. P4, 17-OH-P4, hCG, and inhibin-A) during the early luteal phase in women undergoing IVF treatment with luteal phase support given in the form of exogenous P4 administration and evaluate whether clinical pregnancy rates are related to specific characteristics of the early luteal phase. By including the measurements of 17-OH-P4 and inhibin-A the study will obtain an evaluation of the function of corpora lutea itself independent of the P4 administration provided.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

Study Locations

• Vietnam
  • Tan Binh
    • Ho Chi Minh City, Tan Binh, Vietnam
      • Mỹ Đức Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Vietnamese women who will be indicated for IVF treatment with hCG administration for final oocytes maturation and undergo fresh embryo transfers.

Description

Inclusion Criteria:

• Age 18 - 38
• BMI < 28kg/m2
• Normal ovarian reserve (anti-Müllerian hormone level above 8.93 pmol/L or an antral follicle count of 6 or above within two months prior to stimulation)
• Having 4 to 19 follicles with a diameter of 14mm or above on the day of hCG triggering
• Receiving a standard GnRH-antagonist protocol for ovarian stimulation
• Having indication for fresh embryo transfer
• Willingness to participate in the study, and to disclose any medical conditions to the investigator. The patient must be prepared and willing to comply with the requirements of the protocol.
• The patient should after appropriate oral and written consent understand the study and be informed that she may withdraw consent at any time without prejudice to future medical care.

Exclusion Criteria:

• Previous poor ovarian response (≤ 3 follicles) after appropriate FSH stimulation
• Hyper-response defined as ≥20 follicles ≥14 mm on the day of trigger
• Chronical medical conditions like Diabetes, Crohns disease, Thyroid disease, Hepatitis B, Sexually Transmitted Diseases and simultaneous participation in an interventional clinical trial.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Hormonal levels; Blood samples are collected for analysis of progesterone, hCG, inhibin-A, and 17-OH-Progesterone levels.

Other: Hormonal levels; A total of ten (10) blood samples (2ml/each) will be collected during the study for subsequent analysis of progesterone, hCG, inhibin-A, and 17-OH-progesterone: Day of triggering (before the injection of hCG, appx. 6 pm) Twelve (12 hours) after hCG injection (appx. at 6 am) Twenty-four (24) hours after hCG injection (appx. at 6 pm) Thirty-six (36) hours after hCG injection (appx. at 8 am, 2 hours after OPU) One (1) day after OPU (60h after hCG) (appx. at 6 am) Two (2) days after OPU (84h after hCG) (appx. at 6 am) Three (3) days after OPU 108h after hCG) (appx. at 6 am) Four (4) days after OPU (132h after hCG) (appx. at 6 am) Five (5) days after OPU (156h after hCG) (appx. at 6 am) Six (6) days after OPU (180h after hCG) (appx. at 6 am)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate in relation to the trajectory of progesterone in the early luteal phase	Live birth was defined as the birth of at least one newborn after 24 weeks' gestation that exhibited any sign of life (twins were a single count).	After 24 weeks of gestation
Live birth rate in relation to the trajectory of 17-OH progesterone in the early luteal phase	Live birth was defined as the birth of at least one newborn after 24 weeks' gestation that exhibited any sign of life (twins were a single count).	After 24 weeks of gestation
Live birth rate in relation to the trajectory of hCG in the early luteal phase	Live birth was defined as the birth of at least one newborn after 24 weeks' gestation that exhibited any sign of life (twins were a single count).	After 24 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The clinical pregnancy rate in relation to the trajectory of progesterone in the early luteal phase	Pregnancy with at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity	At 5 weeks after embryo placement
The ongoing pregnancy rate in relation to the trajectory of progesterone in the early luteal phase	Pregnancy with detectable heart rate at 12 weeks' gestation or beyond	At 10 weeks or beyond after the embryo placement
The clinical pregnancy rate in relation to the trajectory of 17-OH progesterone in the early luteal phase	Pregnancy with at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity	At 5 weeks after embryo placement
The ongoing pregnancy rate in relation to the trajectory of 17-OH progesterone in the early luteal phase	Pregnancy with detectable heart rate at 12 weeks' gestation or beyond	At 10 weeks or beyond after the embryo placement
The miscarriage rate in relation to the trajectory of progesterone in the early luteal phase	Pregnancy loss before 12 completed weeks of gestational age	Before 12 weeks of gestation
The miscarriage rate in relation to the trajectory of 17-OH progesterone in the early luteal phase	Pregnancy loss before 12 completed weeks of gestational age	Before 12 weeks of gestation
Live birth rate in relation to the trajectory of inhibin A in the early luteal phase	Will be reported in a separate paper	After 24 weeks of gestation

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital
• Investigators: Principal Investigator: Lan N Vuong, PhD, Mỹ Đức Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: December 28, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 18/20/DD-BV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No