Fertility and Pregnancy in Patients With Classic Congenital Adrenal Hyperplasia (FERTI-HCS)

Classic congenital adrenal hyperplasia (CAH) is a rare genetic endocrine disorder. Its prevalence is around 1/15.000. It results from a deficiency in 21-hydroxylase, an adrenal steroidogenic enzyme involved in the biosynthesis of cortisol and aldosterone. Enzyme deficiency in the steroideogenesis pathway leads to cortisol and aldosterone deficiency of varying severity, and to the accumulation of precursors (17OHP and Progesterone), which are diverted to the production of androgens (Testosterone and D4AD).

There are two clinical forms of classical CAH : the salt wasting form and the simple virilizing form, depending on the degree of aldosterone deficiency.

The clinical signs are adrenal insufficiency and hyperandrogenism. Hyperandrogenism manifests itself during foetal life, and may be responsible for virilization of the external genitalia of a female foetus, of varying severity.

The challenge in managing this condition is to find the right therapeutic balance. Hydrocortisone and fludrocortisone supplementation must be adapted to control adrenal insufficiency, and limit hyperandrogenism. It must be sufficient to avoid episodes of acute adrenal insufficiency, but not excessive to avoid complications secondary to hypercorticism.

During childhood, this balance is necessary for growth and pubertal development. However, this balance is difficult to achieve and maintain over time.

In adulthood, the fertility of patients is an important issue. This one remains poorly understood.

It was only after the introduction of cortisol supplementation in the treatment of CAH in the 1950s that the first pregnancies were described. Since when, due to the rarity of the pathology, the number of pregnancies studied has remained low, and the literature has little hindsight on the subject.

This pathology has long been associated with female infertility, due to many factors : biological, mechanical, psychological and sexual, among others. Biological hyperandrogenism may be responsible for chronic dysovulation, and may render the endometrium unsuitable for embryonic implantation. The virilization of the external genitalia and possible complications of pelvic surgery can be an obstacle to sexuality in these patients. They experience sexual difficulties, particularly during penetrative intercourse. The literature also shows that the majority of these patients are single and that their sexual orientation is more likely to be homosexual. Finally, the desire to have children is less prevalent in these patients than in the general population.

The first published studies on the fertility of CAH patients showed a lower pregnancy rate than the general population, but did not take into account the patient' desire to become pregnant.

In 2009, Casteras et al demonstrated for the first time in a cohort of CAH patients that fecundity is preserved in patients with a desire to become pregnant.

It should be noted that the fertility of patients with CAH may evolve in the coming years in France thanks to the new bioethics law voted in 2021, which now allows unmarried patients and patients in homosexual couples to have access to male gamete donation.

In addition, very little is known about the course of pregnancies in patients with CAH. Few pregnancies have been studied to date.

Hormonal balance during pregnancy if difficult to monitor, given the absence of reliable biological makers during this period. In this context, it is complicated to know the impact of the pathology and its balance on the course of the pregnancy.

The latest articles published on the subject of pregnancy complications are contradictory. Some find an increased risk of gestational diabetes. Others find a higher risk of maternal-fetal infection, low weight for gestational age, or congenital malformations than in general population. The increased risk of miscarriage is debated.

On the other hand, articles are unanimous on the most frequent mode of delivery in this population : in the vast majority of cases, patients give birth by ceasarian section, due to their history of pelvic surgery.

It is in context that we wish through this study to make a point of fertility and pregnancy in patients with classical CAH.

Study Overview

• Status: Completed
• Conditions: Classic Congenital Adrenal Hyperplasia
• Intervention / Treatment: Other: Women patients with classical congenital adrenal hyperplasia

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Endocrinology Department of Louis Pradel Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study will focus on patients in the Endocrinology department of the Louis Pradel Hospital in Bron, suffering from a classic form of Congenital Adrenal Hyperplasia by enzymatic block.

Description

Inclusion Criteria:

for patient :

• Adult patient > 18 years
• Classical congenital adrenal hyperplasia (21-hydroxylase deficiency, 11β-hydroxylase deficiency and 3βHSD2 deficiency)
• Who have indicated that they do not object to participating in the sudy

For partners :

- No objection to the collection of their fertility data

Exclusion Criteria:

• Non classical congenital adrenal hyperplasia
• Classical congenital adrenal hyperplasia due to other enzyme block

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the fertility of classical CAH women patients who had a desire for pregnancy and sought to conceive	Proportion of patients who have had at least one pregnancy, regardless of outcome, among patients who have had a desire for pregnancy and have tried to conceived	At inclusion

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2024
• Primary Completion (Actual): February 16, 2024
• Study Completion (Actual): February 16, 2024

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: pregnancy; fertility; Classic congenital adrenal hyperplasia; fecundity
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: 69HCL23_1153; 2023-A02432-43 (Other Identifier: ID-RCB)

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