Immunomodulatory Effects of Subcutaneous Progesterone in Patients Affected by Autoimmune Diseases

Immunomodulatory Effects of Subcutaneous Progesterone in Patients Undergoing IVF Affected by Autoimmune Diseases

This study evaluates the immunomodulatory effects of subcutaneous progesterone in patients undergoing IVF by determination of anti-nuclear antibodies (ANA),extractable nuclear antigen antibodies (ENA),anti- neutrophil cytoplasmic antibodies(ANCA),anti-DNA antibodies, anti-cardiolipin antibodies (ACA),Lupus anticoagulant antibodies (LAC) and C3 and C4 fractions of complement on the day of beta hCG dosage and during the eigth week of gestation.

Study Overview

• Status: Completed
• Conditions: Autoimmune Diseases; Infertility
• Intervention / Treatment: Drug: aqueous subcutaneous progesterone

Detailed Description

The aqueous progesterone preparation for s.c. injection is the first systemic progesterone of its kind for the provision of luteal phase support (LPS) in patients undergoing IVF.

The the high solubility and rapid absorption of the new preparation are enhanced using cyclodextrins that are starch residues with no therapeutic activity and with a particular molecular structure that closely resembles a 'cap'.

Once absorbed after injection, the progesterone molecule is immediately dissociated from its cyclodextrin 'cap', remaining free in the circulation as if produced endogenously by the ovaries.

In comparison to progesterone-in-oil preparation, the new aqueous solution administered by s.c.route resulted in a 3 fold higher and more rapid progesterone peak serum concentrations.

The immunomodulating effects of progesterone are mediated outside of the pelvic cavity, on the peripheral cell of the immune system. For this reason only the injection procedure has this advantage Furthermore, the faster absorption rate and the higher peak serum concentration should increas the systemic immunomodulatory effect of subcutaneous progesterone compared to the vaginal and intramuscular administration

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Italy
  • Potenza, Italy, 85100
    • Assunta Iuliano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Infertile patients affected by autoimmune diseases undergoing IVF

Description

Inclusion Criteria:

• Infertile patients affected by autoimmune diseases undergoing IVF

Exclusion Criteria:

• infertile patients without autoimmune diseases, fertile patients affected by autoimmune diseases

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients affected by autoimmune diseases; Infertile patients suffering from autoimmune diseases to be subjected to IVF in which the luteal phase has been supplemented with 25 mg /die of aqueous subcutaneous progesterone	Drug: aqueous subcutaneous progesterone; 25 mg/die of aqueous subcutaneous progesterone from the day of oocytes retrieval for two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy Rate percentage, Implantation Rate percentage, Live Birth Rate percentage	number of pregnancies / 100 embryotransfer, number of implanted embryos/ number of embryos trafsferred, number of live birth	12 mounths

Collaborators and Investigators

• Sponsor: San Carlo Public Hospital, Potenza, Italy
• Investigators: Principal Investigator: Assunta Iuliano, MD,PhD, San Carlo Public Hospital, Potenza, Italy

Publications and helpful links

General Publications

• Paulson RJ. Hormonal induction of endometrial receptivity. Fertil Steril. 2011 Sep;96(3):530-5. doi: 10.1016/j.fertnstert.2011.07.1097.
• de Ziegler D, Sator M, Binelli D, Leuratti C, Cometti B, Bourgain C, Fu YS, Garhofer G. A randomized trial comparing the endometrial effects of daily subcutaneous administration of 25 mg and 50 mg progesterone in aqueous preparation. Fertil Steril. 2013 Sep;100(3):860-6. doi: 10.1016/j.fertnstert.2013.05.029. Epub 2013 Jun 24.
• Practice Committee of the American Society for Reproductive Medicine. Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertil Steril. 2015 Apr;103(4):e27-32. doi: 10.1016/j.fertnstert.2014.12.128. Epub 2015 Feb 11.
• Fatemi HM. The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online. 2009;19 Suppl 4:4331.
• Stavreus-Evers A, Mandelin E, Koistinen R, Aghajanova L, Hovatta O, Seppala M. Glycodelin is present in pinopodes of receptive-phase human endometrium and is associated with down-regulation of progesterone receptor B. Fertil Steril. 2006 Jun;85(6):1803-11. doi: 10.1016/j.fertnstert.2005.12.018. Erratum In: Fertil Steril. 2006 Aug;86(2):498. Aghajnova, Lusine [corrected to Aghajanova, Lusine].
• Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril. 2000 Jan;73(1):136-42. doi: 10.1016/s0015-0282(99)00457-4.
• Faas M, Bouman A, Moesa H, Heineman MJ, de Leij L, Schuiling G. The immune response during the luteal phase of the ovarian cycle: a Th2-type response? Fertil Steril. 2000 Nov;74(5):1008-13. doi: 10.1016/s0015-0282(00)01553-3.
• Rier SE. Environmental immune disruption: a comorbidity factor for reproduction? Fertil Steril. 2008 Feb;89(2 Suppl):e103-8. doi: 10.1016/j.fertnstert.2007.12.040.

Helpful Links

• The luteal phase after 3 decades of IVF: what do we know? HM Fatemi, Vol.19 Suppl. 4, 2009 Reproductive BioMedicine Online

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: December 6, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: May 23, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: autoimmune diseases and infertility; luteal supplementation with subcutaneous progesterone; Systemic effect of progesterone
• Additional Relevant MeSH Terms: Immune System Diseases; Urogenital Diseases; Genital Diseases; Infertility; Autoimmune Diseases; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: San Carlo Public Hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We have a register which shows the number of the medical record of the patient
• IPD Sharing Time Frame: 30 years
• IPD Sharing Access Criteria: Archive of Medically Assisted Procreation of San Carlo Hospital
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR