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Ovarian Reserve and Bariatric Surgery

Recruiting
Conditions
Reproductive Health
Bariatric Surgery
Obesity
Fertility
Interventions
Procedure: Bariatric surgery
Registration Number
NCT04583150
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
238
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)

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Obese women with planned surgery (BS group)Bariatric surgeryObese women with planned BS procedure in standard care
Primary Outcome Measures
NameTimeMethod
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 surgeryChange from baseline to 12 months after bariatric surgery (bariatric surgery group) or to 12 months after inclusion (control group)

AMH levels will be measured using the AMH Gen II ELISA (Beckman Coulter, ref A79765) whatever the day of the menstrual cycle

Secondary Outcome Measures
NameTimeMethod
Nutritional status by albumin dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring albumin(g/L) in blood samples

Nutritional status by heamoglobin dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring hemoglobin(g/L) in blood samples

Anti-mullerian hormone (AMH) level evolutionbefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)

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.

Body compositionbefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12 months(control group)

by impedancemetry and/or Dual x-ray absorptiometry (DXA) if possible

Hormonal evaluation of Total testosteronebefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)

Hormonal evaluation is evaluated by measuring Total testosterone (ng/ml) in blood samples

Hormonal evaluation of Sex hormone binding globulinbefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)

Hormonal evaluation is evaluated by measuring Sex hormone binding globulin (SHBG) (mmol/l) in blood samples

Nutritional status by vitamin B1 dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin B1(nmol/L or ng/ml) in blood samples

Nutritional status by vitamin B9 dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin B9(nmol/l) in blood samples

Nutritional status by vitamin B12 dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin B12(pg/ml or pmol/L) in blood samples

Nutritional status by vitamin D dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin D(ng/ml or nmol/L) in blood samples

Nutritional status by vitamin A dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin A(ng/ml or µmol/L) in blood samples

Hormonal evaluation of Follicle Stimulating Hormonebefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)

Hormonal evaluation is evaluated by measuring Follicle Stimulating Hormone (FSH) (IU/l) in blood samples

Hormonal evaluation of estradiolbefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)

Hormonal evaluation is evaluated by measuring estradiol (pg/ml) in blood samples

Hormonal evaluation of luteinizing hormonebefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12, 24 and 36 months (control group)

Hormonal evaluation is evaluated by measuring , luteinizing hormone (LH) (IU/l) in blood samples

Nutritional status by prealbumin dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring prealbumin(g/L) in blood samples

Nutritional status by vitamin B6 dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin B6(nmol/L or ng/ml) in blood samples

Nutritional status by vitamin E dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring vitamin E(mg/L or µmol/L) in blood samples

Nutritional status by Parathyroid hormone dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring Parathyroid hormone (PTH) (pmol/L or pg/mL) in blood samples

Nutritional status by calcemia dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring calcemia(mmol/L or mg/L) in blood samples

Nutritional status by ferritin dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring ferritin(µg/L) in blood samples

Nutritional status by transferrin saturation coefficient dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring transferrin saturation coefficient(%) in blood samples

Nutritional status by zinc dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring zinc(mg/L or µmol/L) in blood samples

Metabolic status by HDL cholesterol dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring HDL cholesterol(mmol/L or g/L ) in blood samples

Sexuality scorebefore surgery, 12, 24 and 36 months after BS (bariatric surgery group) and at baseline and 12,24 and 36 months (control group)

Female Sexual Distress Scale-Revised (sexual quality of life) scale

Nutritional status by selenium dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Nutritional status is evaluated by measuring selenium(µg/L or µmol/L) in blood samples

Metabolic status by fasting blood glucose dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring fasting blood glucose (mmol/L or g/L ) in blood samples

Metabolic status by insulin dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring insulin(µUI/mL) in blood samples

Metabolic status by HbA1c dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring HbA1c(%) in blood samples

Metabolic status by creatinine dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring creatinine(µmol/L or mg/L) in blood samples

Metabolic status by LDL cholesterol dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring LDL cholesterol(mmol/L or g/L ) in blood samples

Metabolic status by Triglycerides dosagebefore and 12, 24 and 36 months after surgery and at baseline and 12 months in controls

Metabolic status is evaluated by measuring Triglycerides(mmol/L or g/L ) in blood samples

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
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)

Trial Locations

Locations (13)

CHU Angers

🇫🇷

Angers, France

AP-HM - Hôpital Nord

🇫🇷

Marseille, 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

CHU Nantes - Hôpital Nord Laennec

🇫🇷

Nantes, France

HCL - Hôpital Lyon -Sud

🇫🇷

Lyon, France

AP-HP - Groupe Hospitalier Pitié Salpêtrière

🇫🇷

Paris, France

CHU Montpellier Hôpital Lapeyronie

🇫🇷

Montpellier, France

AP-HP - Hôpital Europeen Georges Pompidou

🇫🇷

Paris, France

002 CHU Toulouse -Hôpital Rangueil

🇫🇷

Toulouse, France

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