Clinical trial NCT04583150: Ovarian Reserve and Bariatric Surgery
Official title: Evolution of Ovarian Reserve in Severely Obese Women After Bariatric Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Bariatric Surgery
Obesity
Reproductive Health
Fertility
Keywords: Obesity
Bariatric surgery
Gastric bypass
Sleeve
Fertility
Anti-mullerian hormone
Ovarian reserve
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-10-12
Enrollment: 238
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Obese women with planned BS procedure vs. obese women matched for age and BMI without BS procedure.

Brief summary: The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. Severe obesity has negative effects on fertility and on in vitro fertilization (IVF) outcomes, and the weight loss induced by the bariatric surgery (BS) is believed to reverse the deleterious impact of overweight and obesity on female fertility. However, research is limited to retrospective cohort studies, small case-series and case-control studies. Weight reduction has been shown to improve fecundity and hormonal state of a subgroup of obese patients with polycystic ovary syndrome (PCOS). In this population, recent studies have demonstrated an increase of naturally conceived pregnancies following bariatric surgery. However, these studies have evaluated only short-term evolution of ovarian function and not all studies demonstrated improvements in fertility outcomes after BS. Clearly, more studies are needed regarding the effect of BS on obesity-related infertility, and long-term outcome of ovarian function has to be assessed.

Markers of ovarian reserve, including Follicle Stimulating Hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH), have been used to counsel patients regarding in their reproductive outcomes. Serum AMH concentrations remain remarkably stable throughout the menstrual cycle, which is a great advantage over other markers of fertility. Various studies have evaluated the association between AMH and body mass index (BMI) but reported contradictory results. Some of them have reported a significant inverse correlation between AMH and BMI, but others found no relationship between AMH and BMI. Scarce and small preliminary studies have been performed to evaluate AMH changes after surgical weight loss and showed a decrease in serum AMH.

Detailed description: Medical files of volunteers obese women consulting an endocrinologist nutritionist or a gynaecologist in each center will be screened and women fitting the inclusion criteria will be proposed to participate in the study. These women will be enrolled and matched with obese women with planned bariatric surgery prospectively. The matching for age (± 1 year) and BMI category (BMI 35-39.9 kg/m², 40-49.9 kg/m² and ≥ 50 kg/m²) of each woman in the surgery group with a control woman will be performed globally, i.e. two matched women could belong to the same center or two different centers.

This is a national prospective multicentre cohort study. Obese women with planned BS, matched for presurgical age and BMI with women with no planned BS.

Subjects with planned bariatric surgery will be recruited in the nutrition departments. All consecutive eligible patients will be considered for inclusion.

Obese women with no planned bariatric surgery will be recruited in the same centers than the corresponding women with planned bariatric surgery, but two matched women can belong to two different centers.

All subjects will be followed 36-42 months according to the delay between inclusion and BS, and AMH levels will be measured at baseline or preoperative time, 12, 24 and 36 months after baseline for controls and after BS for operated women.

Eligibility criteria: Inclusion Criteria:

Obese women with planned surgery (BS group)

1. Obese women with an indication of bariatric surgery (BMI ≥ 35 kg/m² with an obesity related comorbidity or BMI ≥ 40 kg/m²)
2. Age 18 to 37 years (inclusion possible until the day before the 37th birthday)
3. No pregnancy project in the next 12 months
4. Signed informed consent
5. Affiliated to The French social security except patient on AME (state medical aid)

Obese women with no planned surgery (control group)

1. Obese women with BMI ≥ 35 kg/m²
2. Age 18 to 37 years (inclusion possible until the day before the 37th birthday)
3. No pregnancy project in the next 12 months
4. Signed informed consent
5. Affiliated to the French social security except patient on AME (state medical aid)
6. Matched for age and BMI category (35-39.9 kg/m², 40-49.9 kg/m² and ≥ 50 kg/m²) with an operated woman
7. No bariatric surgery project in the next 12 months

Exclusion Criteria:

For both groups : Obese women with planned bariatric surgery (BS group) and obese women with no planned surgery (control group):

1. Medical condition known to alter ovarian reserve (previous oophorectomy, ovarian surgery, chemotherapy, pelvis or hypothalamic radiotherapy, known premature ovarian insufficiency ...)
2. Contraceptive with antigonadotropic action during the month before inclusion
3. Pregnant or lactating woman
4. HIV infection
5. Previous bariatric surgery
6. Expected follow up less than 3 years
7. Absolute contraindication for bariatric surgery (vital risk, anaesthetic contraindication, non stabilized psychiatric disorder, substance addiction)

Primary outcomes:
measure: Compare anti-mullerian hormone (AMH) levels in obese women before bariatric surgery and 12 months after the surgery, and at baseline and 12 months in women who did not undergo surgery
timeFrame: Change from baseline to 12 months after bariatric surgery (bariatric surgery group) or to 12 months after inclusion (control group)
Secondary outcomes:
measure: Anti-mullerian hormone (AMH) level evolution
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
measure: Body composition
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12 months(control group)
measure: Hormonal evaluation of Total testosterone
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Hormonal evaluation of Sex hormone binding globulin
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Hormonal evaluation of Follicle Stimulating Hormone
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Hormonal evaluation of luteinizing hormone
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Hormonal evaluation of estradiol
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Nutritional status by albumin dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by prealbumin dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by heamoglobin dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin B1 dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin B6 dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin B9 dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin B12 dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin D dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin E dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by vitamin A dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by Parathyroid hormone dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by calcemia dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by ferritin dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by transferrin saturation coefficient dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by zinc dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Nutritional status by selenium dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by fasting blood glucose dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by insulin dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by HbA1c dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by HDL cholesterol dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by LDL cholesterol dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by Triglycerides dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Metabolic status by creatinine dosage
timeFrame: before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
measure: Number of pregnancies and time to pregnancy (TTP)
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
measure: Sexuality score
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
measure: Sexuality score
timeFrame: before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
measure: Ultrasound (US) pelvic sonography with follicular antral count (AFC)
timeFrame: before and at 12, 24 and 36 months after surgery, and at baseline and 12 months in controls
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand -Site Gabriel Montpied
city: Colombes
country: France
facility: AP-HP - Hôpital Louis Mourier
city: Dijon
country: France
facility: CHU Dijon Bourgogne - Hôpital Le Bocage Sud
city: Grenoble
country: France
facility: CHU Grenoble-CSO Grenoble-Arc Alpin
city: Lille
country: France
facility: CHRU Lille -Hôpial Claude Huriez
city: Lyon
country: France
facility: HCL - Hôpital Lyon -Sud
city: Marseille
country: France
facility: AP-HM - Hôpital Nord
city: Montpellier
country: France
facility: CHU Montpellier Hôpital Lapeyronie
city: Nantes
country: France
facility: CHU Nantes - Hôpital Nord Laennec
city: Paris
country: France
facility: AP-HP - Groupe Hospitalier Pitié Salpêtrière
city: Paris
country: France
facility: AP-HP - Groupe Hospitalier Pitié Salpêtrière
city: Paris
country: France
facility: AP-HP - Hôpital Europeen Georges Pompidou
city: Toulouse
country: France
facility: 002 CHU Toulouse -Hôpital Rangueil
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: CIANGURA Cécile, MD
role: PRINCIPAL_INVESTIGATOR
References: