Ovarian Reserve and Bariatric Surgery

Obesity Clinical Trial

— BARIAOVO  

Official title:

Evolution of Ovarian Reserve in Severely Obese Women After Bariatric Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04583150
• Other study ID #: APHP180620
• Status: Recruiting
• Start date: December 3, 2020
• Est. completion date: March 2028

Study information

• Verified date: February 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: CIANGURA Cécile, MD
• Phone: 01 42 17 57 71
• Email: cecile.ciangura[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 238
• Est. completion date: March 2028
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bariatric Surgery
• Fertility
• Obesity
• Reproductive Health

Intervention

Procedure:
• Bariatric surgery
Bariatric surgery : sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB)

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Clermont Ferrand -Site Gabriel Montpied	Clermont-Ferrand
France	AP-HP - Hôpital Louis Mourier	Colombes
France	CHU Dijon Bourgogne - Hôpital Le Bocage Sud	Dijon
France	CHU Grenoble-CSO Grenoble-Arc Alpin	Grenoble
France	CHRU Lille -Hôpial Claude Huriez	Lille
France	HCL - Hôpital Lyon -Sud	Lyon
France	AP-HM - Hôpital Nord	Marseille
France	CHU Montpellier Hôpital Lapeyronie	Montpellier
France	CHU Nantes - Hôpital Nord Laennec	Nantes
France	AP-HP - Groupe Hospitalier Pitié Salpêtrière	Paris
France	AP-HP - Groupe Hospitalier Pitié Salpêtrière	Paris
France	AP-HP - Hôpital Europeen Georges Pompidou	Paris
France	002 CHU Toulouse -Hôpital Rangueil	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AMH levels will be measured using the AMH Gen II ELISA (Beckman Coulter, ref A79765) whatever the day of the menstrual cycle	Change from baseline to 12 months after bariatric surgery (bariatric surgery group) or to 12 months after inclusion (control group)
Secondary	Anti-mullerian hormone (AMH) level evolution	Because AMH level is known to decrease with age and the speed of this evolution is mostly unknown in obese women, the deterioration of ovarian reserve in obese women who undergo surgery will be defined according to the natural evolution of AMH level observed in the control group of obese women without bariatric surgery. In operated women, a deterioration will be defined as a decrease of more than 2 standard deviation of the mean decrease observed in non-operated women.	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
Secondary	Body composition	by impedancemetry and/or Dual x-ray absorptiometry (DXA) if possible	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12 months(control group)
Secondary	Hormonal evaluation of Total testosterone	Hormonal evaluation is evaluated by measuring Total testosterone (ng/ml) in blood samples	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Hormonal evaluation of Sex hormone binding globulin	Hormonal evaluation is evaluated by measuring Sex hormone binding globulin (SHBG) (mmol/l) in blood samples	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Hormonal evaluation of Follicle Stimulating Hormone	Hormonal evaluation is evaluated by measuring Follicle Stimulating Hormone (FSH) (IU/l) in blood samples	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Hormonal evaluation of luteinizing hormone	Hormonal evaluation is evaluated by measuring , luteinizing hormone (LH) (IU/l) in blood samples	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Hormonal evaluation of estradiol	Hormonal evaluation is evaluated by measuring estradiol (pg/ml) in blood samples	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Nutritional status by albumin dosage	Nutritional status is evaluated by measuring albumin(g/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by prealbumin dosage	Nutritional status is evaluated by measuring prealbumin(g/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by heamoglobin dosage	Nutritional status is evaluated by measuring hemoglobin(g/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin B1 dosage	Nutritional status is evaluated by measuring vitamin B1(nmol/L or ng/ml) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin B6 dosage	Nutritional status is evaluated by measuring vitamin B6(nmol/L or ng/ml) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin B9 dosage	Nutritional status is evaluated by measuring vitamin B9(nmol/l) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin B12 dosage	Nutritional status is evaluated by measuring vitamin B12(pg/ml or pmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin D dosage	Nutritional status is evaluated by measuring vitamin D(ng/ml or nmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin E dosage	Nutritional status is evaluated by measuring vitamin E(mg/L or µmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by vitamin A dosage	Nutritional status is evaluated by measuring vitamin A(ng/ml or µmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by Parathyroid hormone dosage	Nutritional status is evaluated by measuring Parathyroid hormone (PTH) (pmol/L or pg/mL) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by calcemia dosage	Nutritional status is evaluated by measuring calcemia(mmol/L or mg/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by ferritin dosage	Nutritional status is evaluated by measuring ferritin(µg/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by transferrin saturation coefficient dosage	Nutritional status is evaluated by measuring transferrin saturation coefficient(%) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by zinc dosage	Nutritional status is evaluated by measuring zinc(mg/L or µmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Nutritional status by selenium dosage	Nutritional status is evaluated by measuring selenium(µg/L or µmol/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by fasting blood glucose dosage	Metabolic status is evaluated by measuring fasting blood glucose (mmol/L or g/L ) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by insulin dosage	Metabolic status is evaluated by measuring insulin(µUI/mL) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by HbA1c dosage	Metabolic status is evaluated by measuring HbA1c(%) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by HDL cholesterol dosage	Metabolic status is evaluated by measuring HDL cholesterol(mmol/L or g/L ) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by LDL cholesterol dosage	Metabolic status is evaluated by measuring LDL cholesterol(mmol/L or g/L ) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by Triglycerides dosage	Metabolic status is evaluated by measuring Triglycerides(mmol/L or g/L ) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Metabolic status by creatinine dosage	Metabolic status is evaluated by measuring creatinine(µmol/L or mg/L) in blood samples	before and 12, 24 and 36 months after surgery and at baseline and 12 months in controls
Secondary	Number of pregnancies and time to pregnancy (TTP)		before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)
Secondary	Sexuality score	Female Sexual Function Index scale	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
Secondary	Sexuality score	Female Sexual Distress Scale-Revised (sexual quality of life) scale	before surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)
Secondary	Ultrasound (US) pelvic sonography with follicular antral count (AFC)		before and at 12, 24 and 36 months after surgery, and at baseline and 12 months in controls