Clinical trial NCT05034250: Iron Status in Female Infertility and Recurrent Miscarriage
Official title: Iron Status in Women With Infertility and Controls - a Prospective Case-control Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Recurrent Miscarriage
Infertility
Iron-deficiency
Keywords: Iron status
Recurrent Miscarriage
Infertility
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Vifor Pharma, Inc.
First posted: 2021-09-05
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women will be invited to participate by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Clinical Division of Gynecologic Endocrinology and Reproductive Medicine, using the above-mentioned criteria in the course of their admission to the outpatient clinics. Potential participants are informed about the procedure, clinical relevance and the balance of risk and benefits incurred through study participation. Patients willing to participate will express this through written affirmation (a "consent form"). Healthy controls will not receive compensation.

Brief summary: Multiple studies suggest a link between the iron status and the development of the endometrium. Therefore, a sufficient iron supply seems to relevant for female fertility and reproduction.

To gain further insight on the effects of iron status on female fertility, a prospective study on infertile women und women with recurrent miscarriage will be conducted. In these, the iron status will be evaluated in detail. In addition, a control group of healthy women without infertility will be enrolled.

Detailed description: The high importance of sufficient iron supply for the human body is without doubt. Notably, it has also been suggested that iron was a central resource in female reproduction.

Women are more prone to iron deficiency than men. It has been stated frequently that blood loss during menstruation was the major cause of lower iron levels in women. On average, women lose about 16 mg of iron for the average menstrual period. This is in line with several studies which demonstrated that women who had menorrhagia were at a higher risk of anemia and iron deficiency anemia. However, the link between menstruation-caused blood loss and iron status is less clear. In previous studies, it was found that higher hemoglobin was associated with a thicker endometrium. An improved body condition, as measured by iron status, might allow women to grow a thicker endometrium despite the fact that a thicker endometrium was associated with greater blood loss.

In addition, reproductive hormones are also implicated in iron status and are also responsible for the sexual dimorphism in iron levels in humans. For example, androgens stimulate the formation of red blood cells and are responsible for their higher hemoglobin levels. The role of estrogens is less clear, since studies have been contradicting. However, studies on the relationship between contraceptive pills and iron status may have provided the biggest clue to the effects of estrogen on iron physiology. Hormonal contraceptive use seems to raise iron stores. Notably, recent evidence suggests that estrogen itself, which also includes the estrogen in contraceptive pills, helps increase absorption of iron.

It has been mentioned that the iron status could be linked with fertility. As part of a larger study on iron supplementation and hair loss, the circumstances of seven women who became pregnant during the supplement intervention has been investigated. Despite the small number of women, this study suggests an intriguing link between iron status and ability to conceive. In addition, a larger, 8-year prospective study of 18,555 premenopausal women in the United States found that women who consumed iron supplements had a significantly lower risk of infertility than women who did not consume iron supplements. Together with the above mentioned observation that women with an improved iron status were able to grow a bigger endometrium, it seems reasonable to assume an influence of iron status on female fertility. Hypothetically, this could lead either to infertility/sterility or to recurrent miscarriage. Notably, one recent small study demonstrated no difference in iron levels between women with recurrent miscarriage and controls. Notably, other parameters of the iron status were not assessed. However, epidemiologic data on iron status and female fertility are scarce. Thus, a prospective study on infertile women und women with recurrent miscarriage will be conducted. In these women, the iron status will be evaluated in detail. In addition, a control group of healthy women without infertility will be enrolled.

Eligibility criteria: Women with infertility

Inclusion criteria:

* The patient suffers from primary or secondary infertility, defined as the inability to conceive despite frequent unprotected sexual intercourse for at least 12 months.
* The patient has given her written informed consent after detailed information on the study by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna.
* The patient is \>18 and \<40 years old.

Exclusion criteria:

* Inflammatoric bowel disease, cardiac insufficiency, chronic kidney disease, any malignant diseases.
* Polycystic ovary syndrome.
* There is no "informed consent".

Women with recurrent miscarriage

Inclusion criteria:

* The patient suffers from recurrent miscarriage, defined as three or more consecutive miscarriages before the 20th gestation week with the same partner.
* The patient has given her written informed consent after detailed information on the study by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna.
* The patient is \>18 and \<40 years old.

Exclusion criteria:

* Inflammatoric bowel disease, cardiac insufficiency, chronic kidney disease, any malignant diseases.
* Polycystic ovary syndrome
* There is no "informed consent".

Healthy controls

Inclusion criteria:

* The woman does neither suffer from infertility/sterility nor from recurrent miscarriage and is also otherwise healthy with regular cycles.
* The patient has given her written informed consent after detailed information on the study by medical professionals at the Department of Obstetrics and Gynecology of the Medical University of Vienna.
* The patient is \>18 and \<40 years old.

Exclusion criteria:

* Inflammatoric bowel disease, cardiac insufficiency, chronic kidney disease, any malignant diseases.
* Polycystic ovary syndrome
* There is no "informed consent".

Primary outcomes:
measure: Serum ferritin in µg/L
timeFrame: 6 months
Secondary outcomes:
measure: serum iron in µg/dL
timeFrame: 6 months
measure: transferrin in mg/dL
timeFrame: 6 months
measure: transferin-saturation in %
timeFrame: 6 months
measure: C-reactive protein mg/dL
timeFrame: 6 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Johannes Ott, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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