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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Antichlamydial Antibodies, Chlamydia Trachomatis Infection, Infertility, Tubal Factor Infertility

Intervention / Treatment
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* Diagnostic Test: antichlamydial antibody test
* Drug: treatment of infertility with ART


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: antibody positive (CAT+)<br>patients found positive for one of the assayed antichlamydial antibodies | Diagnostic Test: antichlamydial antibody test<br>* 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.<br>Drug: treatment of infertility with ART<br>* 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.<br>* Other names: Procedure;|
| Other: antibody negative (CAT-)<br>women with negative antichlamydia antibody test | Diagnostic Test: antichlamydial antibody test<br>* 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.<br>Drug: treatment of infertility with ART<br>* 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.<br>* Other names: Procedure;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antichlamydial antibodies, in vitro fertilization, ovarian stimulation, tubal factor infertility