A hydatidiform molar pregnancy happens when tissue that normally forms the placenta instead becomes a growth, that triggers symptoms of pregnancy. A hydatidiform mole is a benign tumor of the root system (trophoblast) of the embryo which under normal conditions develops into the placenta which connects the baby to the mother. About 1 out of 2,000 women with early pregnancy symptoms will have a molar pregnancy. It is approximately twice as common in women of Asian descent. The condition requires urgent treatment and follow-up to avoid serious complications that can involve invasion of the uterine wall and surrounding structures (i.e. invasive mole or chorioadenoma destruens) or malignant change (choriocarcinoma). In more than 25% of early pregnancies there will be some vaginal bleeding. About one half of these end up by miscarrying. In the remaining half, the bleeding subsides and the pregnancy continues to evolve such that most will culminate in a healthy live birth. In less than 2% of cases of such bleeding the cause of early pregnancy bleeding is hydatidiform mole (molar) pregnancy. With molar pregnancy, the roots of the trophoblast (chorionic villi) undergo cystic degeneration and when the woman bleeds, these cystic structures are passed in dark blood, giving rise to the common description of “white currents floating in red currant jelly”. In non-molar pregnancies, an inevitable miscarriage almost invariably presents with flattening or declining blood pregnancy hormone (i.e. hCG) levels. Conversely, with hydatidiform mole the blood hCG concentration is usually elevated continues to rise. In addition, the woman will often experience exaggerated pregnancy symptoms (e.g. pernicious vomiting, very frequent urination and bloating) and lower abdominal cramping. On examination, she will often be found to have a markedly elevated blood pressure. On abdominal or vaginal examination here uterus is commonly enlarged beyond that which can be explained on the basis of the duration of pregnancy. Ultrasound examination usually (but not invariably) reveals a hazy, so called “snow storm pattern” and the absence of a conceptus. There are two types of hydatidiform mole, complete or partial

• Complete Hydatidiform mole:  Like normal pregnancies the complete mole has 46 chromosomes (two sets of 23), i.e. it is diploid.. However unlike with normal fertilization where one set of chromosomes comes from the mother and the other set from the father, with a complete molar pregnancy both sets of chromosomes come from the father. This is the result from duplication of a sperm’s chromosomes after it has fertilized an “inactive egg”. Since an embryo that has a YY karyotype is not viable, the chromosome gender of the molar pregnancy is invariably XX (female). Accordingly, if with IVF, one avoids transferring an embryo that by preimplantation genetic diagnosis (PGD) is found to be female (XX) and selectively transfers only male (XY) embryos the possibility of a complete molar pregnancy can be virtually eliminated. A complete molar pregnancy can result from fertilization of an “inactive egg” by 2 separate spermatozoa. Injection of a single sperm by ICSI avoids the latter from occurring altogether. In <10% of cases a complete Hydatidform molar pregnancy can be inherited due to a mutation (not yet clearly identified) involving chromosome 19. In such cases molar pregnancies can occur repetitively and the mole can have an XX or an XY chromosomal configuration. It should be borne in mind however, that not all repetitive molar pregnancies are due to this mutation. Complete molar pregnancies can also run in families (e.g. in sisters). The true incidence of this genetic mutation is still unknown. This situation cannot be identified by PGD.

• Partial (placental) molar pregnancies are usually triploid [i.e. their cells contain three sets of (23each) chromosomes]. Thus with partial moles, the sex chromosome configuration will be XXY or XYY. Partial Hydatidform molar can therefore be avoided through selectively transferring embryos where through PGD triploidy has been excluded.

More than 80% of molar pregnancies are benign (noncancerous). Treatment involves complete emptying of the uterus as soon as the diagnosis is made. Even in cases where a spontaneous passage of the molar tissue appears to be complete. The reason is to avoid the development of an invasive mole (chorioadenoma destruens), where the uterine wall is permeated by remaining tissue and to limit the development of choriocarcinoma (where the molar tissue becomes malignant). In the vast majority of properly managed cases however, outcome after treatment is usually excellent. Close follow-up with serial quantitative blood hCG testing, ultrasound and/or Magnetic Resonance Imaging (MRI) is essential. After treatment, the woman must use very effective contraception for at least 6 to 12 months so as to avoid pregnancy in order to allow for proper follow-up. Choriocarcinoma is a very malignant tumor that invades the uterus and can spread rapidly via the blood system to bone, lungs, brain and other sites. Fortunately choriocarcinoma does respond well to hysterectomy and removal of ovaries with aggressive, selective chemotherapy. While Molar pregnancy is not commonly seen in patients undergoing IVF, it does occur and the vigilant doctor should always be on the look-out for it. As indicated, in cases in which a woman seeking IVF has a family history of the condition or has had a prior molar pregnancy herself, PGD can provide an efficient way to all but prevent this condition from occurring.