Cohort Study Investigating the Association Between Antichlamydial Antibody Positivity and ART Outcomes in Women With TFI

Cohort Study Investigating the Association Between Antichlamydial Antibody Positivity and Efficiency of Treatment With Assisted Reproduction Technologies (ART) in Women With Tubal Factor Infertility

In a prospective cohort study investigators will examine characteristics and clinical outcomes of treatment with ART in women with tubal factor infertility (TFI) with regard to seropositivity to antichlamydial antibodies.

Study Overview

• Status: Active, not recruiting
• Conditions: Infertility; Chlamydia Trachomatis Infection; Antichlamydial Antibodies; Tubal Factor Infertility
• Intervention / Treatment: Diagnostic test: antichlamydial antibody test; Drug: treatment of infertility with ART

Detailed Description

At the first day of stimulation blood analyses for immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) to major chlamydial antigens (anti-C.trachomatis), major outer membrane protein (MOMP) and plasmid-encoded protein (pgp3) will be performed for patients found eligible for the study.

According to the result of chlamydial antibody test (CAT) participants will be divided into two groups: group A - women with at least one of antibodies detected (CAT+); Group B - seronegative subjects (CAT-).

Women of both groups will undergo a conventional ovarian stimulation (COS) with GnRH antagonist and daily gonadotropin administration at the dose of 150-300 international unit (IU).

Retrieved oocytes following fertilization (conventional IVF or ICSI) will be cultured to Day 3-5 in vitro; ultrasound guided single or double embryo transfer will be performed; remaining embryos of eligible quality will be vitrified.

Patients will be followed up to live birth. Frozen/thawed embryo transfers (FET) will be performed until at least one live birth (≥20 weeks of gestation) occurred or all embryos resulting from the mentioned assisted ovarian stimulation were used.

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 199034
    • D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 41 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Tubal factor infertility diagnosed by laparoscopy;
• Female age between 20-41 years;
• BMI 17,5-35 kg/m2;
• Early follicular phase follicle stimulating hormone (FSH) ≤15 IU/L
• Presence of viable spermatozoa in partner's sperm;
• Signed informed consent.

Exclusion Criteria:

• previous ovarian surgery;
• endometriosis;
• antimullerian hormone (AMH) level ≤0,3 ng/ml;
• hyper- or hypogonadotropic ovarian failure;
• severe male factor infertility;
• Pre-existing medical condition preventing or interfering with IVF treatment: any clinically significant systemic disease; inherited or acquires thrombophilia and thromboembolism; endocrine or metabolic abnormalities; moderate or severe impairment of renal or hepatic function; any oncological diseases in anamnesis; known history of recurrent miscarriage, abnormal karyotype of both partners; currently active pelvic inflammatory disease;
• Abnormal IVF screening tests: Papanicolaou (PAP) smear, Syphilis, HIV 1&2, Hepatitis B, Hepatitis C, Chlamydia, and Gonorrhea;
• Presence of uterine pathology: Asherman's Syndrome, endometrial polyps, nodus form of adenomyosis or uterine fibroids ≥3 mm in diameter;
• Visualization of ovarian cysts ≥25 mm, endometriomas or hydrosalpinx;
• One or more follicles ≥8 mm at the start of the COS protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: antibody positive (CAT+); patients found positive for one of the assayed antichlamydial antibodies	Diagnostic test: antichlamydial antibody test; At the first day of stimulation blood analyses for IgG, IgA and IgM (ELISA) to major chlamydial antigens (anti-C.trachomatis), major outer membrane protein (MOMP) and plasmid-encoded protein (pgp3) will be performed for patients found eligible for the study.; Drug: treatment of infertility with ART; COS in gonadotropin-releasing hormone (GnRH) antagonist protocol with IVF/ICSI, fresh ET and, if no pregnancy occurred, frozen/thawed ET (for all embryos resulting from this COS) will be performed.; Other Names: Procedure
OTHER: antibody negative (CAT-); women with negative antichlamydia antibody test	Diagnostic test: antichlamydial antibody test; At the first day of stimulation blood analyses for IgG, IgA and IgM (ELISA) to major chlamydial antigens (anti-C.trachomatis), major outer membrane protein (MOMP) and plasmid-encoded protein (pgp3) will be performed for patients found eligible for the study.; Drug: treatment of infertility with ART; COS in gonadotropin-releasing hormone (GnRH) antagonist protocol with IVF/ICSI, fresh ET and, if no pregnancy occurred, frozen/thawed ET (for all embryos resulting from this COS) will be performed.; Other Names: Procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of oocytes (COCs)	obtained during oocyte pick-up (OPU)	2-4 weeks after after assignment (at oocyte recovery day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of low prognostic patients	according to POSEIDON criteria low prognostic patients will be divided to 4 groups	up to 1 week after assignment
Duration of stimulation	total days of COS: from the first gonadotropins administration to ovulation triggering	2-4 weeks after assignment
Number/rate of participants with poor or suboptimal response to COS	≤5, 5-9 cumulus-oocyte complexes (COCs) at OPU respectively	2-4 weeks after after assignment (at oocyte recovery day)
Number / rate of mature (MII) oocytes	assessment is done only for ICSI cycles	2-4 weeks after after assignment (at oocyte recovery day)
Fertilization rate	number / rate of two-pronuclear zygotes (2PN) on day 1 after fertilization	at day 1 after oocyte recovery
Number / rate of best and good quality embryos per transfer	embryo quality assessment according to known classifications	3-5 weeks after after assignment (at ET day)
Implantation rate	ratio of the number of intrauterine gestational sac (at 5-6 weeks of gestation) to the number of transferred embryos	3-4 weeks after fresh or frozen/thawed ET
clinical pregnancy rate	presence of intrauterine gestational sac at transvaginal ultrasound at 5-6 weeks of gestation or 5-6 weeks after starting the intervention; measured per embryo transfer	5-6 weeks after starting the stimulation or 3-4 weeks after frozen/thawed ET

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	at least one live born baby at ≥20 weeks of gestation; measured per oocyte aspiration, fresh embryo transfer	up to 3 years after assignment
Cumulative live birth rate	at least one live born baby at ≥20 weeks of gestation from ART aspiration cycle, including fresh and frozen/thawed ET, resulting from assisted ovarian stimulation until one live birth occurred or all embryos were used	up to 3 years after assignment
Cost-effectiveness of COS	ratio of total cost of stimulation, FETs to the number of patients with clinical pregnancy	up to 3 years after assignment
Cycle cancellation rate	during COS (no response), at OPU (premature ovulation, absence or degradation of COCs), during in vitro cultivation and thawing (fertilization failure, inadequate embryo quality), other reasons (adverse events, hyper stimulation syndrome, withdrawal);	up to 2 years after assignment

Collaborators and Investigators

• Sponsor: D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 25, 2019
• Primary Completion (ACTUAL): January 30, 2020
• Study Completion (ANTICIPATED): October 30, 2021

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (ACTUAL): October 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 23, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: in vitro fertilization; ovarian stimulation; Antichlamydial antibodies; tubal factor infertility
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: D-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: at the end of recruitment ICF and brief CRF will be shared. At the study completion - CSR and SAP will be uploaded
• IPD Sharing Time Frame: at the study completion for 1 year
• IPD Sharing Access Criteria: 30 random CRFs will be shared, more by request
• IPD Sharing Supporting Information Type: SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No