Effect of Fasting on ICSI Outcomes in Poor Responders

This study is a prospective, randomized controlled trial conducted at the In Vitro Fertilization ( IVF) center of the Department of Obstetrics & Gynecology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Egypt, from October 2018 to September 2019, to determine the clinical effect of fasting on ICSI outcomes in poor responders 360 participants will be randomized withdrawing closed envelopes for each patient into group A and group B .

Group (A): patients will have periodic fasting for 4 weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. Group (B): no fasting, patients will have usual balanced diet as 3 meals and 2 snacks all over the day. Both groups should take adequate water and non calorie beverages intake daily (2-3 liters).

All patients will start the ICSI cycle using the same treatment protocol. Primary outcome is clinical pregnancy rate per cycle. Secondary outcomes include Body mass index (BMI) and waist/hip ratio (WHR), fasting insulin , fasting plasma glucose, Homeostatic model assessment (HOMA) index, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2, Days of stimulation , dose of gonadotrophins, number of M II oocytes retrieved, number of grade1and 2 embryos, number of frozen embryos, freeze all cycles, Ovarian Hyperstimulation syndrome (OHSS), Chemical pregnancy rate, clinical pregnancy, twins, abortion, ectopic pregnancy, preterm labour, live birth rate

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Behavioral: Fasting; Behavioral: No fasting

Detailed Description

This study is a prospective, single-blinded (to the outcomes assessor), randomized controlled trial conducted at the In Vitro Fertilization ( IVF) center of the Department of Obstetrics & Gynecology, Kasr El-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, Egypt, from October 2018 to September 2019, to determine the clinical effect of fasting on ICSI outcomes in poor responder patients. Ethical committee approval was obtained. The study will include 360 infertile patients with poor ovarian reserve (POR )diagnosed by low Antral follicle count (AFC)( less than 5 follicles), Elevated basal follicle-stimulating hormone (FSH) (more than 10 IU/mL) and low anti-Mullerian hormone (AMH)(less than 1.5 ng/ml), previous POR (≤three oocytes with a conventional stimulation protocol). Women with diabetes, thyroid disorder or other endocrine dysfunctions, uterine abnormalities were excluded.Also severe oligo-astheno-teratozoospermia or azospermia are excluded.

All patients are informed about the study and consent is given by those who accept to participate.

Careful history taking include infertility type, duration , cause, obstetric history, medical and surgical history and demographic distribution is taken. Full physical examination and 2 dimensional (2D) transvaginal sonography (TVS) are done on day 2 to 5 of menses to assess antral follicle count, uterus and adnexa . Body mass index (BMI) and waist/hip ratio (WHR) are calculated, Blood samples are taken for fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL),AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2) All 360 participants will be randomized withdrawing closed envelopes for each patient into group A and group B .

Group (A): patients will have periodic fasting for 4 weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. Group (B): no fasting, patients will have usual balanced diet as 3 meals and 2 snacks all over the day. Both groups should take adequate water and non calorie beverages intake daily (2-3 liters) Subjects are instructed to wait for spontaneous menses. The next visit is scheduled on day 2 of next cycle when transvaginal ultrasound is done to confirm that endometrial thickness <5mm, no ovarian cyst by ultrasound. Body mass index (BMI) and waist/hip ratio (WHR) are calculated. Blood samples are taken for fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2),and then antagonist protocol is followed. Gonadotropins as Intramuscular (I.M.) injections of 150-300 (International units) I.U. of highly purified Human Menopausal Gonadotropins daily (Merional, 75 I.U. /vial, IBSA). and Urofollitropin or highly purified human follicle stimulating hormone(Fostimon®, 75 I.U. /vial, IBSA) are give in a ratio of 1:1.The dose is adjusted according to the age, BMI, Antral follicle count (AFC), serum levels of AMH, FSH and ovarian response.

On the sixth day of stimulation , a visit is scheduled to assess the ovarian response ( folliculometry) by TVS. Gonadotrophin releasing hormone antagonist (GnRH antagonist) which is Cetrorelix 0.25mg ( Cetrotide®, 0.25 mg/ vial, Merck Serono, is filled and mixed with diluent from a prefilled syringe with a 20 gauge needle) is given subcutaneously (S.C.) by 27-gauge needle starting from the 6th day of stimulation (fixed antagonist protocol).

Next visits are every other day for follow up using the TVS. The trigger by Human Chorionic Gonadotrophin (HCG)10000 I.U., I.M. ( Pregnyl, Organon) is given when at least 3 follicles reach 18mm in mean diameter or more and E2 level is less than 2500 pg/ml. Ovum retrieval is done 34 hours after HCG injection and embryo transfer using Wallace catheter on day 2 to 3. Luteal support includes natural Progesterone 400 mg 1x2 as rectal suppository, Folic acid 0.5 mg orally once daily, Amoxicillin-Clavulanic Acid 1gm 1x2x7 orally, Progesterone 100 I.M. injections daily for 10 days, Acetylsalicylic Acid (75 mg) orally once daily Quantitative ß- HCG in serum after is done after 14 days of embryo transfer.TVS is performed to detect clinical pregnancy at 6-7 weeks of gestation.

Primary outcome is clinical pregnancy rate per cycle. Secondary outcomes include Body mass index (BMI) and waist/hip ratio (WHR), fasting plasma glucose, lipid profile ( Triglycerides (TGs), total cholesterol, High density Lipoprotein (HDL), Low density Lipoprotein (LDL), AntiMullerian Hormone (AMH), Basal Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2, Days of stimulation , dose of gonadotrophins, number of M II oocytes retrieved, number of grade1and 2 embryos, number of frozen embryos, freeze all cycles, Ovarian Hyperstimulation syndrome (OHSS), Chemical pregnancy rate, clinical pregnancy, twins, abortion, ectopic pregnancy, preterm labour, live birth rate

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11956
    • KasrELAiniH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

The study will include:

infertile patients with poor ovarian reserve (POR )diagnosed by low Antral follicle count (AFC)( less than 5 follicles), Elevated basal follicle-stimulating hormone (FSH) (more than 10 IU/mL) and low anti-Mullerian hormone (AMH)(less than 1.5 ng/ml), previous POR (≤three oocytes with a conventional stimulation protocol).

Women with diabetes, thyroid disorder or other endocrine dysfunctions, uterine abnormalities were excluded.Also severe oligo-astheno-teratozoospermia or azospermia are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fasting group; Patients will have periodic fasting for 4 weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. They should take adequate water and non calorie beverages intake daily (2-3 liters)	Behavioral: Fasting; Periodic fasting last for 4weeks prior to the treatment cycle. The fasting method involves daily fasts of 14-16hours and restrict eating to an 8-10 hour "eating window" as 2-3 or more meals of balanced diet. Patients should take adequate water and non calorie beverages intake daily (2-3 liters).; Other Names: Periodic fasting
Other: Non fasting group; no fasting, patients will have usual balanced diet as 3 meals and 2 snacks all over the day. They should take adequate water and non calorie beverages intake daily (2-3 liters)	Behavioral: No fasting; Patients will not fast . But they will take balanced food and drink 2 to 3 liters of water and non caloric drinks all the day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical pregnancy rate per cycle	detection of gestationalsac, embryonal pole and fetal pulsations by ultrasonography	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass index	The weight in kilograms divided by the squared height in meters	4 weeks of fasting
Waist/Hip ratio	The ratio of waist circumference in centimeters to the hip circumference in centimeters	4 weeks of fasting
Number of days of stimulation with gonadotrophins	Days of stimulation with gonadotrophins	6 weeks
Number of ampoules of gonadotrophins	total number of ampoules of gonadotrophins	6 weeks
number of M II oocytes retrieved	number of M II oocytes retrieved	6 weeks
number of grade1and 2 embryos	number of grade1and 2 embryos	6-7 weeks
number of frozen embryos	number of frozen embryos	6-7 weeks
number of freeze all cycles	total number of freeze all cycles	6 weeks
number of cancelled cycles	total number of cancelled cycles	6 weeks
Rate of chemical pregnancy rate	number of cases with positive pregnancy test with no clinical pregnancy	10 weeks
Rate of twin pregnancy	presence of two gestational sacs detected by ultrasonography	10 weeks
Rate of abortion per cycle	number of abortions clinically detected per cycle	10-24 weeks after embryo transfer
Rate of ectopic pregnancy	the presence of gestational sac outside the uterine cavity detected by ultrasound	10 weeks
Rate of preterm labour	labour after 20 weeks of gestation and before completed 37 weeks of gestation	After 24 weeks of start of study
live birth rate	live birth rate	After40 weeks of start of study

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: Amira S Dieb, MD, KasralainiH

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: September 26, 2018
• First Submitted That Met QC Criteria: October 17, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Infertility; Intracytoplasmic sperm injection; fasting; Poor ovarian reserve
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 88766808

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