Melanoma risk after in vitro fertilization: A review of the literature.

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

Short- and long-term effects of ovulation induction.

Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone is reviewed. The short- and long-term consequences of these therapies are discussed in detail.

A normal cumulative conception rate after human pituitary gonadotropin.

Forty consecutive women were treated with human pituitary gonadotropin to induce ovulation. Thirty-seven patients (93%) ovulated and thirty (75%) conceived on at least one occasion. The cumulative conception rate for the series equaled that of the general population. Women with a past history of anorexia nervosa had the shortest average time to pregnancy. Of patients who did not conceive, four represented failures of patient selection in that they withdrew from treatment for a variety of psychiatric and social reasons, and six represented failures of treatment, not becoming pregnant despite the induction of ovulation. It is concluded that realistic goals for a contemporary human gonadotropin program include induction of ovulation in all patients and a cumulative conception rate equal to that of the general community.

Quintuplet pregnancies.

Five quintuplet pregnancies, following induction of ovulation with clomiphene and HMG-HCG, are the subject of this communication. In 3 women, pregnancy was associated with ovarian overstimulation, and two patients required emergency surgery because of torsion of an ovarian cyst. Two women aborted in mid-trimester, while the other 3 delivered by cesarean section at 33-35 wk gestation. 15 babies were born, weighing 700-2200 g. 8 infants suffered from respiratory distress syndrome and 5 babies were born with correctable malformations. 13 newborns survived, and all are mentally and physically well-developed. Four of the 5 women conceived again. The management of the patients during multiple gestation and the outcome of pregnancy are discussed.

Studies of the coagulation and fibrinolytic systems in hyperstimulation syndrome after administration of human gonadotropins.

Coagulation and fibrinolytic profiles have been studied in two groups of sterility patients receiving low dosage regimens of human gonadotropins for ovarian stimulation. This investigation was prompted by a report of two patients with severe episodes of intravascular coagulation associated with periods of "hyperstimulation" from these drugs. No statistically significant changes were found as a result of administration of one ampoule of human menopausal (HMG) or pituitary gonadotropins (HPG) for 8 days followed by 9000 units of human chorionic gonadotrophin (HCG). A course of 2-3 ampoules HMG on alternate days for longer periods of time prior to administration of HCG also failed to produce significant alterations of the coagulation or fibrinolytic mechanisms. In two patients with severe hyperstimulation there were elevated levels of factor V, platelets, fibrinogen, profibrinolysin, and fibrinolytic inhibitors. Generation of thromboplastin was also increased when plasma was diluted one to fifty in the thromboplastin generation test. These results suggest a possibly increased coagulation potential in patients with "hyperstimulation syndrome" but not in those receiving the low dosage regimens of human gonadotropins more commonly used for ovarian stimulation at the present time.

[Occlusion of the middle cerebral artery after induction of ovulation with gonadotropins]. / Occlusion de l'artère cérébrale moyenne lors d'une induction de l'ovulation par les gonadotrophines.

A case of occlusion of the middle cerebral artery during a treatment with gonadotropin is reported. Such cases are unusual when one considers that these treatments are widely used. They occur after a markek ovarian hyperstimulation syndrome. Treatment is purely preventive with clinical, laboratory and ultrasonic examinations before injection of beta-HCG.

[Ovarian hyperstimulation syndrome. Notes on the physiopathology and treatment apropos of 3 cases]. / Syndrome d'hyperstimulation ovarienne commentaires sur la physiopathologie et le traitement, à propos de 3 observations

Hyperstimulation appeared in one case on the 10th 11th day after ovulation, allowing by its presence the very precocious diagnosis of successful fecondation. The study of blood coagulation revealed that hypercoagulability was mainly related to hyperactivity of the thrombocytes and of the coagulation proteins. The pathogenesis of the syndrome is discussed. Increase in the permeability of the capillary vessels and hypovolemia seem to be responsible for the main accidents. Unfortunately as we have no real mean of decreasing the permeability of the capillary vessels, the treatment can be directed only against hypovolemia and its results. The infusion of macromolecular fluids, the restriction of sodium and water intake, together with the prescription of spironolactone have been successfully employed in those three cases.

[Ultrasonic follow-up check of overstimulation by gonadotrophin therapy (author's transl)]. / Ultraschallverlaufskontrollen bei Uberstimulierung unter Gonadotropintherapie.

The risk of overstimulation is implied in any therapy, using gonadotrophin to induce ovulation. Cystic changes were recorded from the ovaries in 30 of 119 gonadotrophin treatments. Early detection of overstimulation was accomplished by ultrasonic follow-up checks and daily oestradiol assay.

Twin pregnancies following induction of ovulation: a literature review.

A literature review of the occurrence of multiple pregnancies associated with artificial induction of ovulation is reported. This report considers three treatment schedules: (1) clomiphene citrate; (2) human pituitary gonadotrophin with human chorionic gonadotrophin; and (3) human menopausal gonadotrophin with human chorionic gonadotrophin. The majority of the increase in twinning is related to hyperstimulation of the ovary by these medications, resulting in dizygotic twinning. The true incidence of twin pregnancy cannot be calculated because the vital statistics of all nations report live birth rates. Increased rates of fetal wastage, late abortion and prematurity associated with the occurrence of multiple pregnancies are overlooked by these statistics. The increased incidence of twinning appears to be related to the type and dosage of medication used, and the patient's underlying problem.

Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin: a second case.

A 44 year old female presented with a progressive cerebellar disturbance approximately 13 years after receiving human pituitary derived gonadotrophin injections as a treatment for infertility. The patient died approximately nine months later. Creutzfeldt-Jakob disease was confirmed at necropsy. This is the second reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin.

Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease.

The spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) has been transmitted to man via administration of growth hormone and gonadotropin extracted from large pooled batches of human cadaveric pituitary glands. In the UK, 1908 individuals were exposed to potentially contaminated growth hormone, of whom 6 have so far manifested CJD. Examination of the prion protein genes of all these cases and of a single case of gonadotropin-related CJD showed that 4 had the uncommon valine 129 homozygous genotype indicating genetic susceptibility to prion infection. Such genetic susceptibility may be important in the aetiology of sporadic CJD disease.

Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin.

A forty-year-old female presented with an unsteady gait 13 years after receiving an eight-month course of human pituitary-derived gonadotrophin injections as treatment for infertility. Over the next ten months the patient subsequently developed generalised myoclonic jerks and dementia and finally died. Neuropathological examination revealed changes in the brain consistent with Creutzfeldt-Jakob disease. This is the first reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin.