Medically Assisted Fertilization Techniques in Systemic Immunoreumatologic Diseases

Assessment of Maternal-fetal Outcome in Pregnancy From Medically Assisted Fertilization Techniques in Women With Systemic Immunoreumatologic Diseases

Systemic rheumatological diseases often occur in young women of childbearing age and can therefore impact fertility. There are diseases, such as arthritis, which present no contraindication to assisted reproductive techniques (ARTs), because there is no influence on the disease itself if the disease activity at conception is stable. On the other hand, patients suffering from connective tissue diseases, primarily Systemic Lupus Erythematosus (SLE) and patients suffering from primary or SLE-related Anti-Phospholipid Antibody Syndrome (APS), deserve more targeted therapies both in the context of ARTs and in the ensuing pregnancy.

To evaluate the response to ARTs in patients with systemic rheumatological diseases, both in terms of reactivation of the underlying pathology and in terms of ARTs outcome.

Study Overview

• Status: Recruiting
• Conditions: Rheumatic Diseases; Pregnancy Complications; Pregnancy, High Risk; Fertility Disorders; Immunologic Disease
• Intervention / Treatment: Other: collection and analysis of treatments and procedures already performed by normal clinical practice

Detailed Description

According to standard clinical practice related to medically assisted procreation treatments, for controlled ovarian stimulation aimed at oocyte recovery, patients underwent therapy with recombinant, biosimilar, or purified human gonadotropins and eventual suppression of spontaneous ovulation with gonadotropin-releasing hormone stimulating antagonist (gnRH-antagonist), and this information will therefore be recorded. The subsequent final induction of oocyte maturity can be by purified human chorionic gonadotropin (hCG), by gonadotropin-releasing hormone stimulating hormone analog (GnRHa), or by the combination of the two, and this information will therefore also be recorded. Similarly, therapies routinely administered for endometrial preparation and luteal support during embryo transfer procedures will also be recorded (transdermal estradiol, oral estradiol; transvaginal micronized progesterone; subcutaneous progesterone). With regard to the types of PMA used, patients may have undergone homologous or heterologous procedures based on the patient's own choice and specialist indications. The IVF technique is an in vitro fertilization that consists of the union of the egg with the sperm in the laboratory -in vitro- for the purpose of obtaining already fertilized embryos to be transferred into the maternal uterus. The ICSI technique consists of intracytoplasmic sperm injection and involves the insemination of an oocyte by micro-injection of a single sperm directly into it.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Valentina Canti, MD; Phone Number: +390226436095; Email: canti.valentina@hsr.it
• Study Contact Backup: Name: Patrizia Rovere Querini, PhD, MD; Phone Number: +390226436095; Email: rovere.patrizia@hsr.it

Study Locations

• Italy
  • Milan, Italy
    • Recruiting
    • San Raffaele Hospital
    • Contact: Patrizia Rovere Querini, PhD,MD; Phone Number: +390226433065; Email: rovere.patrizia@hsr.it
    • Contact: Valentina Canti, MD; Phone Number: +390226436095; Email: canti.valentina@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Approximately 500 women with a definite diagnosis of systemic immunoreumatologic disease according to the criteria classificatory in place in normal clinical practice who underwent one or more PMAs between January 2000 and April 2021 will be enrolled from all participating centers.

Pathologies examined will be:

APS defined according to Sapporo criteria, SLE, AR, SpA, SScl, SS, PM-DM, systemic vasculitis of large- and small-medium caliber defined according to EULAR/ACR criteria.

Description

Inclusion Criteria:

• Patients diagnosed with systemic immunoreumatologic disease such as SLE, APS, RA, SpA, SclS, SS, PM-DM, vasculitis
• patients who have performed one or more PMAs between January 2000 and April 2021
• patients who had their last follow-up by February 2022

Exclusion Criteria:

• Patients diagnosed with only one organ autoimmunity (e.g., diabetes mellitus I, thyroiditis of Hashimoto's, celiac disease or chronic inflammatory bowel disease in the absence of systemic disease associated);
• patients with severe renal failure, significant pulmonary hypertension or cardiomyopathy severe.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

pregnant patients with systemic rheumatological diseases; pregnant patients with systemic rheumatological diseases undergoing assisted fertilization techniques

Other: collection and analysis of treatments and procedures already performed by normal clinical practice; The patients' anthropometric variables; laboratory test results; PMA techniques (types of fertilization/drugs used for stimulation) and the outcome of the eventual pregnancy (ongoing treatment during the pregnancy itself, development of maternal/fetal complications, such as hypertension, preeclmpsia, thrombotic events, renal failure, disease flare, neonatal outcome) and data on the type of ovarian stimulation drug treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantify the risk of flare-ups of underlying immunoreumatologic disease and possible occurrence of complications during the procedure or during PMA pregnancies.	Disease flare-up will be assessed by measuring clinical parameters and antibody values ANA, ENA, SSA_SSB, antiDNA (U.A.), PMA, post PMA, post pregnancy complement. Complications will be evaluated in terms of maternal/fetal outcome such as hypertension, preeclmpsia, thrombotic events, renal failure, disease flare during pregnancy.	Within six months after the end of the study
To quantify the risk of flare-ups of underlying immunoreumatologic disease and possible occurrence of complications during the procedure or during PMA pregnancies.	Disease flare-up will be assessed by measuring clinical parameters and antibody values, MB2GPI, GB2GPI (UA/mL), PMA, post PMA, post pregnancy complement. Complications will be evaluated in terms of maternal/fetal outcome such as hypertension, preeclmpsia, thrombotic events, renal failure, disease flare during pregnancy.	Within six months after the end of the study
To quantify the risk of flare-ups of underlying immunoreumatologic disease and possible occurrence of complications during the procedure or during PMA pregnancies.	Disease flare-up will be assessed by measuring clinical parameters and antibody values, LAC (Microun./mL), PMA, post PMA, post pregnancy complement. Complications will be evaluated in terms of maternal/fetal outcome such as hypertension, preeclmpsia, thrombotic events, renal failure, disease flare during pregnancy.	Within six months after the end of the study
To quantify the risk of flare-ups of underlying immunoreumatologic disease and possible occurrence of complications during the procedure or during PMA pregnancies.	Disease flare-up will be assessed by measuring clinical parameters and antibody values MACA, GACA, (GPL/MPL/APL unità) PMA, post PMA, post pregnancy complement. Complications will be evaluated in terms of maternal/fetal outcome such as hypertension, preeclmpsia, thrombotic events, renal failure, disease flare during pregnancy.	Within six months after the end of the study

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Investigators: Principal Investigator: Patrizia Rovere Querini, PhD, MD, IRCCS Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2022
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Musculoskeletal Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Pregnancy Complications; Immune System Diseases; Rheumatic Diseases; Collagen Diseases
• Other Study ID Numbers: PMA_AD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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