Clinical trial NCT05858307: Clinical Application of Serum Anti-Müllerian Hormone (AMH) Measurements
Official title: Clinical Application of Serum Anti-Müllerian Hormone (AMH) Measurements
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Anti-Müllerian Hormone
Polycystic Ovarian Syndrome
Premature Ovarian Insufficiency
Fertility Issues
Keywords: Anti-Müllerian hormone
Polycystic Ovarian Syndrome
Premature Ovarian Insufficiency
Assisted Reproductive Technology treatment
Predictive value
Reproductive outcomes
AMH
PCOS
POI
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2023-05-15
Enrollment: 300
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 44
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The following clients will be included in our study population.

* Women attending the Paediatric and Adolescent Gynaecological Clinic and Gynaecological Endocrine Clinic of in the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital for the management of PCOS and POI
* Women attending the Assisted Reproductive Technology (ART) Unit of The Chinese University of Hong Kong for ART treatment

Brief summary: This study aims to assess the association of Anti-Müllerian hormone (AMH) with polycystic ovarian syndrome, premature ovarian insufficiency and fertility. The main objectives include the following:

1. To study the level of serum AMH in women with PCOS and to evaluate the utility of serum AMH in the diagnosis of PCOS.
2. To evaluate the level of serum AMH in women with POI and to evaluate the utility of serum AMH in the management of POI.
3. To evaluate the associations of basal AMH level with FSH level and AFC respectively for women undergoing ART treatment.
4. To determine the optimal regimen of gonadotropin for ovarian stimulation for women undergoing ART treatment.
5. To evaluate the predictive value of serum AMH in reproductive outcomes including oocyte quality, embryo quality, pregnancy loss, clinical pregnancy and live birth rate in women undergoing ART treatment.

Detailed description: \[Background\] Anti-Müllerian hormone (AMH), which level can be assessed in serum, is a product of follicular granulosa cells of preantral and small antral follicles in the ovary. AMH expression increases prior to follicle-stimulating hormone (FSH)-dependent selection (follicles up to 8 mm) and rapidly decreases thereafter (follicles \> 8 mm. Thus, serum AMH level is a reliable marker of functional ovarian reserve as it reflects the pool of growing follicles. Since AMH is relatively cycle independent and has no inter-rater variability, it is considered to be a more reliable biomarker of ovarian function across an array of clinical conditions when compared with follicle-stimulating hormone (FSH) and antral follicular count (AFC).

\<Association between AMH and polycystic ovarian syndrome (PCOS)\> PCOS is a common endocrine disorder that causes menstrual irregularity and hyperandrogenism in women. It affects approximately 4-20% of women of reproductive age. Women with PCOS have been shown to have elevated AMH levels when compared with women without PCOS as there is an increased number of ovarian follicles in PCOS. Therefore, AMH is being increasingly recognised as a marker for the diagnosis of PCOS. However, a specific cutoff value is yet to be determined. When the issue is addressed, serum AMH levels could potentially replace ultrasound in the diagnosis of PCOS as ultrasound is more costly and less accessible.

\<Association between AMH and premature ovarian insufficiency (POI)\> POI is defined as the cessation of ovarian function before the age of 40 years. Timely diagnosis is important in order to appropriately counsel and treat the patients with POI.

Prompt initiation of hormone replacement therapy is vital to minimise the risk of long-term health complications including osteoporosis and premature cardiovascular disease. AMH levels were significantly low to undetectable in women with POI. Since AMH is independent of the timing in a menstrual cycle, the measurement may be beneficial in the phase of menstrual irregularity and could potentially help to assess the progression of ovarian senescence.

\<Associations between AMH and Fertility\> Serum AMH level is an important indicator of women's ovarian reserve and a crucial tool in assisted reproductive technology (ART) for the evaluation of women's fertility. A recent systematic review concluded that basal serum AMH is a strong pretreatment predictor of poor response to controlled ovarian stimulation (COS) and correlates with the risk of ovarian hyperstimulation syndrome. As such, clinicians can individualise the stimulation protocols to optimise the ovarian response. In addition, AMH-based prognostication counselling can be provided to patients with realistic expectation regarding the ART outcomes.

Ovarian reserve has a well-established positive correlation with pregnancy outcome. However, current evidence of AMH in the prediction of reproductive outcome following ART treatment remains controversial. Therefore, there is a need to study the predictive value of AMH on pregnancy outcome in women undergoing ART.

\[Hypothesis\]

1. Serum AMH level is elevated in women with PCOS.
2. Serum AMH level is very low or undetectable in women with POI.
3. Serum AMH level has a significant correlation with FSH and AFC in women undergoing ART treatment.
4. Serum AMH level can predict reproductive outcomes following ART treatment.

\[Study design\] This is a prospective observational study.

\[Methods\] Investigators will collect data from patients who undergo management for PCOS and POI in the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital from 2022 to 2026. For patients undergoing investigation of PCOS and POI, routine venous blood tests for AMH and hormonal profile including FSH, luteinizing hormonal (LH), oestradiol (E2) levels will be obtained. For patients undergoing ART treatment, routine venous blood tests for AMH and hormonal profile, and transvaginal ultrasound for AFC will be arranged to assess the patients' ovarian reserve prior to the commencement of treatment. Patients will be recruited and consent will be obtained for the storage of any remaining serum from the blood tests. The stored blood samples will then be retrieved for this study.

\[Data processing and analysis\] Data analysis will be performed using the Statistical Packages of Social Sciences for Windows (SPSS, Inc). Data will be presented by percentage, mean and standard deviation, and median where appropriate. Comparisons between groups will be carried out by Student T test/Mann-Whitney U test for continuous variables and Chi-square/Fisher's exact test for categorical data. Two-tailed P\<0.05 will be considered significant.

\[Sample size\] All patients fulfilling the inclusion criteria attending the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital from 2022 to 2026 will be recruited. The sociodemographic records of the participants including their menstrual history, routine hormonal results, ovarian reserve assessment and ultrasound assessment of AFC will be obtained. Metabolic screening results and ART treatment records and subsequent laboratory and reproductive outcome will be obtained if necessary.

Eligibility criteria: Inclusion Criteria:

* Women attending the Paediatric and Adolescent Gynaecological Clinic and Gynaecological Endocrine Clinic of in the Department of Obstetrics and Gynaecology at the Prince of Wales Hospital for the management of PCOS and POI
* Women attending the Assisted Reproductive Technology (ART) Unit of The Chinese University of Hong Kong for ART treatment

Exclusion Criteria:

* Women with age \<10 or ≥45
* Current or past diseases affecting gonadotropin, sex steroid secretion, clearance and excretion

Primary outcomes:
measure: Serum anti-Müllerian hormone (AMH) (pmol/L)
timeFrame: Within 1 to 2 months after the day of recruitment
Secondary outcomes:
measure: Type of gonadotropin used for ovarian stimulation
timeFrame: From the first 1 day to last 1 day of ovarian stimulation during ART treatment
measure: Total gonadotropin dose used for ovarian stimulation
timeFrame: On the last 1 day of ovarian stimulation during ART treatment
measure: Number of oocytes retrieved
timeFrame: On the 1 day of oocyte retrieval during ART treatment
measure: Serum follicle stimulation hormone (FSH) (IU/L)
timeFrame: On the first 1 day of ovarian stimulation during ART treatment
measure: Serum luteinising hormone (LH) (IU/L)
timeFrame: On the first 1 day of ovarian stimulation during ART treatment
measure: Serum estradiol (pmol/L)
timeFrame: On the first 1 day of ovarian stimulation during ART treatment
measure: Antral follicle count (AFC)
timeFrame: On the first 1 to 4 days of ovarian stimulation during ART treatment
measure: Clinical pregnancy rate
timeFrame: 6 to 7 weeks of gestation
measure: Live birth rate
timeFrame: from 24 weeks of gestation up to 40 weeks
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: PUI WAH JACQUELINE CHUNG
role: PRINCIPAL_INVESTIGATOR
References: