Iron Deficiency Anemia as a cause of Infertility

Anemia is defined as the reduction in total red cell number, HB, Hct% or circulating red cell mass. Anemia is not a diagnosis, it is a sign of underlying disease. Iron deficiency anemia is one of the most diseases worled wild. WHO has estimated that approximately 30% of the worled population are affected with Fe deficieny anemia.

Although anemia can cause infertility, there have not been enough studies to conclusively link infertility problems and anemia at this moment in time. There was a study that found a possible link between Fe deficiency anemia and infertility associated with ovarian failure in females not taking Fe suplement. Fe deficiency anemia is implicated in premature babies and low birth weight as well.

The primary function of RBCs is to deliver O2 to tissues, ineffective erythropoiesis secondary to Fe deficiency results in decreased circulating red cell number as well as their hemoglobin content that ultimately impaire tissue O2- supply and results in hypoxia.

Gonads are one of the best example of rapidly dividing cells that require high blood as well as enough O2 supply in order to maintain a delicate balance between cell proliferation, differentiation, and apoptosis.

In males, spermatogenesis is a complex process occuring in the seminiferous tubules in testis that are kept 2-7 ͦ C below body core temperature, and proceeds with a blood and O2 supply that is fairly independent of changes in other vascular beds in the body. Despite this apparently well-controlled local environment, chronic hypoxia can result in changes in blood flow, nutrients, and O2 supply along with increased local temprature that induce deletrious effects on Leydig cell function and spermatogenesis and may lead to male subfertility and infertility possibly through germ cell apoptosis and DNA damage manifested as revesible oligospermia, reduction in sperm motility and deacrease in plasma testosterone.

Stages of Fe deficiency

I- Depletion of iron stores

1- decreased serum ferritin.

2- normal serum Fe.

II- Iron deficient erythropoiesis

1- decreased serum ferritin.

2- decrease serum Fe.

3- decrease serum transferrin saturation.

4- increase serum transferrin receptor.

5- increased red cell protopofyrin

6- normal HB, MCV, MCH and MCH.

III- Iron deficiency anemia

1- decreased serum ferritin.

2- decreased serum iron.

3- decresed serum transferrin saturation.

4- increased serum transferrin receptors, TIBC and red cell protoporphyrin.

5- decreased hemoglobin, MCV, MCH and increase RDW.

Causes of iron deficiency anemia

Diagnosis of iron deficiency anemia

I- Clinical features

Clinical manifestations of Fe deficiency anemia are secondary to tissue hypoxia and compansatory mechanisms initiated to correct anemia. There is poor correlation between severity of symptoms and blood hemoglobin concentration.

In addition to general symptoms of anemia including fatigue, dyspnea and palpitation, there are specific symptoms such as headache, parasthesia and burning sensation of the tongue that are symptoms of Fe deficiency rather than anemia. Pica (craving to eat ice, clay, dirt and chalk) is a classical manifestaion of Fe deficiency.

Physical findings in Fe deficiency includes pallor, glossitis, angular stomatitis, koilonichia, pharyngeal webs, papllidema and impaired mental functions in children.

II- Laboratory diagnosis

1-Complete blood count and PB smear examination:

↓HB, ↓RBCs, ↓MCV, ↓MCH, ↑RDW

Microcytic hypocromic anemia, anisocytosis, poikilocytosis (target cells, tear drops, leptocytes), and anisochromia.

Reticulocytes may be increased specially in patients have chronic blood loss but still low for hemoglobin level, may be normal or there may be reticulocytopenia in case of sever Fe deficiency.

Corrected reticulocyte count: reticulocyte coun X patient Hct/45

WBC count may be normal but leucopenia may be present which is unrelated to the degree of anemia, occasinal hypersegmented neutrophils.

Trombocytosis usually occurs in about 50-70% of adult cases with Fe deficiency anemia, especially those in active bleeding, in infants and children, the incidence of thrombocytopenia is less than and thrombocytosis and is associated with more sever anemia.

2- Bone marrow aspiration and cytological examination:

BMA is not required for diagnosis of Fe deficiency anemia. BM show mild hypercellularity due to moderate erythroid hyperplasia, erythropoiesis is micronormoblastic with erythroblasts smaller than normal with scanty cytoplasm, and cytoplasmic dyserythropoiesis in the form ragged cytoplasm, cytoplasmic vacuolation and intercytoplasmic bridging. Giant metamyelocytes may be present, but granulopoiesis is normal. Thrombopoiesis is normal to active in cases with chronic blood loss.

BM Fe stain ranging from deceased to complete absence of iron stores.

3- Other laboratory investigations:

A- Serum iron and TIBC:

Reference range for srum iron is 60-180 Ug/dl and for TIBC the range is 250-410 Ug/dl.

In iron deficiency anemia serum iron decreased and TIBC increased.

Serum iron concentration show diurnal variations with hieghest levels in the morning, so specimens should be collected in the morning and oral iron therapy should be discontinued 24 hours before sample is withdrawn.

A normal serum iron and TIBC do not rule out iron deficiency anemia in cases with HB level is above 9g/dl in females and 11g/dl in males.

B- Serum ferritin:

Normal serum ferritin ranges from 10-500 ng/ml.

Serum ferritin may be decreased early in iron deficiency before HB level is decreased. The coexistance of an inflammatory condition with iron deficiency which often occur serum ferritin level may rise to normal level, so the combination of ESR or CRP may improve the detection of iron deficiency.

C- Serum transferrin receptors:

Circulating serum transferrin receptor concentrations (CD79) increase in tissue iron deficiency reflecting the degree of iron deficient erythropoiesis. There is no difference between healthy males and females as regard serum receptor concentration.

4- Free Erythrocyte protoporphyrin:

Free erythrocyte protoporphyrin levels normally is less than 100 Ug/dl packed RBCs. Ed levels are seen in iron deficiency anemia.