Fibrinogen is a clotting factor Ithat is synthesized by the liver and plays a key role in hemostasis by promoting clot formation ,platelet aggregation and fibrinolysis[5, 12]. It is also a 340KDa myosin that plays an important role in placenta formation during pregnancy[12, 13]. Its normal concentration in plasma is 150-350mg/dl, with a half life period is 3-4days[14, 15]. FIB is a dimer molecule composed of three polypeptide chains Aα, Bβ and ʏ，encoded by FGA，FGB，FGG on chromosome 4 respectively[8, 14]. Congenital hypofibrinogenemia is a rare autosomal inherited disease defined as FIB<150mg/dl[3, 5] and it’s the heterozygote state. Diagnosis is not easy because of the rarity of this disease. Acquired hypofibrinogenemia or afibrinogenemia such as liver disease should be first excluded. Second, ask about family history and then rely on the results of laboratory tests( FIB decreases, BT, APTT, PT, TT all extend, but it can be corrected by fibrinogen)[4, 16]. Clinical manifestations of hypofibrinogenemia may be asymptomatic, bleeding( umbilical cord bleeding, nosebleed, menorrhagic, gastrointestinal bleeding, joint bleeding, musle hematoma, intracranial bleeding and even spontaneous splenic rupture) or thrombogenesis. Patients with hypofibrinogenemia are prone to spontaneous abortion, placental abruption and postpartum hemorrhage during pregnancy[3, 5]. In normal women, plasma FIB level increases after pregnancy to maintain placental integrity, so patients need more fibrinogen as the pregnancy progresses[3, 5]. Treatment depends on the patient’s condition. If patients don’t have any symptoms they don’t need any treatment because unnecessary blood transfusions can cause infections and allergic reactions[4, 8]. Antifibrinolytic can be used for minor bleeding. Fibrinogen replacement can be used in patients with moderate to severe bleeding, in pregnant women or in patients prior to surgery[5, 13]. FIB should be maintained 50-100mg/dl for patients with bleeding tendency[11, 15] and 60-100mg/dl for patients with pregnancy. Patients with hypofibrinogenemia are prone to bleeding after 5 weeks of gestation and spontaneous abortion after 6-8 weeks of gestation. Studies have shown that starting FRT after 5 weeks of gestation still carries a risk of genital bleeding so it is recommended that FRT should be started before pregnancy. FIB should be maintained at 100-200mg/dl for patients undergoing major surgery[10, 15]. Fibrinogen levels need to be monitored daily after FRT, as 20%-30%patients will develop blood clots[10, 15]. Although there is no evidence suggest that FRT is associated with the formation of clots, we all agree that the formation of clots is associated with some predisposition( FRT, infection, pregnancy) . There is no clear treatment or prevention program for thrombotic hypofibrinogenemia, and some scholars believe that heparin can be prophylactic used after FRT[8, 13]. Fibrinogen concentrate is the best choice: 1. Although the price of fresh frozen plasma and cryoprecipitate is lower, larger amounts are needed, especially for pregnant women, which can lead to fluid overload and cardiopulmonary strain. 2. Fibrinogen concentrate does not transmit the disease, fresh frozen plasma and cryopolytes contain proteins that are not needed by patients, which can affect the formation of clots and cause allergic reactions[3, 13-15]. The amount of fibrinogen can be calculated by formula: ( target FIB level-measured FIB level) ÷ 1.7× weight( kg) [5, 13]. For this patient with hypofibrinogenemia, 8000-10000u HCG was injected subcutaneously 36 hours prior to egg retrieval. Elevated HCG increases the risk of thrombogenesis, so we didn’t get as much fibrinogen supplementation as the literature suggested when we did FRT and only got to 88mg/dl.
IVF with hypofibrinogenemia is a very rare case. There were no abnormal conditions such as genital bleeding or placental abruption during treatment and pregnancy. In 2017, the patient had a full-term cesarean section at a local hospital, and both mother and child were in good condition.