Moshe Ben-Ami

Activated Protein C Resistance and Factor V Leiden Mutation can be Associated with First‐ as well as Second‐Trimester Recurrent Pregnancy Loss

PROBLEM: To examine whether the occurrence of activated protein C resistance (APCR) and factor V Leiden mutation differs in women with first‐ compared to women with second‐trimester unexplained recurrent pregnancy loss. METHOD OF STUDY: Seventy eight consecutive women with two or more unexplained post‐embryonic recurrent pregnancy losses and 139 fertile women with at least one successful pregnancy and no abortions were prospectively investigated for APCR and the factor V Leiden mutation. No women were pregnant at the time of investigation. APCR was defined as APC–sensitivity ratio (APC–SR) of ≤2.0. All patients with an APC–SR ≤2.4 were investigated for the factor V Leiden mutation. Women in this study were divided into three groups. Group A included only women with a history of recurrent first‐trimester embryonic loss (37 women) and Group B included women with second‐trimester abortions with or without additional first‐trimester abortions (41 women). Group C included the controls (139 women). RESULTS: APCR and factor V Leiden mutations were significantly more prevalent in all recurrent pregnancy loss patients in this study as compared to controls, 38% (30/78) and 19% (15/78) in contrast to 8% (11/139) and 6% (8/139), respectively. All three groups in the study were comparable regarding age, parity, and number of living children, whereas Groups A and B were also comparable regarding gravidity. Mean APC–SRs were significantly higher in Group C as compared to Groups A and B. The incidence of APCR was significantly higher in Groups A and B, as compared to controls, 27 and 49% in contrast to 8%, respectively. Moreover, the incidence of the factor V Leiden mutation was significantly higher in Groups A and B as compared to Group C, 16 and 22% as distinct from 6%, respectively. The incidence of APCR was higher in Group B as compared to Group A, 49% in contrast to 27%, with borderline significance; however, the factor V Leiden mutation did not significantly differ between the two groups. CONCLUSIONS: APCR and factor V Leiden are associated with unexplained recurrent pregnancy loss. The occurrence of APCR and factor V Leiden seems to be linked to post‐embryonic first‐trimester as well as second‐trimester recurrent pregnancy loss. The significance of acquired, non‐heritable APCR in recurrent fetal loss patients, especially in the second‐trimester aborters, is still to be determined.

The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis.

OBJECTIVE To estimate whether the risk of neonatal thyrotoxicosis was related to the value of maternal thyroid‐stimulating immunoglobulin in women with Graves disease. METHODS The records of pregnant women undergoing testing for thyroid‐stimulating immunoglobulin over a 10‐year period were analyzed. Neonatal thyrotoxicosis was defined as the presence of tachycardia, goiter, hydrops, tremulousness, voracious appetite, irritability, cardiomegaly, or congestive heart failure, with elevated thyroid hormone levels. The relationship between maternal thyroid‐stimulating immunoglobulin values and the development of thyrotoxicosis was examined. The sensitivity, specificity, and positive and negative predictive values were calculated using an arbitrarily chosen cutoff for thyroid‐stimulating immunoglobulin. RESULTS Twenty‐nine women with a history of Graves disease and positive thyroid‐stimulating immunoglobulin values were available for analysis. Of the 35 live births, there were six cases of neonatal thyrotoxicosis (17.1%). A maternal thyroid‐stimulating immunoglobulin value at least 5 index units predicted neonatal thyrotoxicosis with a sensitivity of 100%, specificity of 76.0%, positive predictive value of 40.0%, and negative predictive value of 100%. CONCLUSION Pregnancies complicated by high values of maternal thyroid‐stimulating immunoglobulin appear to be at risk of developing neonatal thyrotoxicosis.

The effectiveness of spectral and color Doppler in predicting ovarian torsion. A prospective study.

We evaluated the effectiveness of color and spectral Doppler examination of the ovarian vasculature flow, using transvaginal sonography (TVS) in 65 women prior to laparoscopy due to suspected ovarian torsion. There were 15 cases of ovarian torsion. In all of them, a pathology was detected by the color and spectral Doppler examination. Of the 50 patients without torsion at laparoscopy, one had abnormal Doppler studies. Color and spectral Doppler can demonstrate the presence or absence of arterial and venous flow in cases of suspected torsion of the ovary.

The combination of magnesium sulphate and nifedipine: a cause of neuromuscular blockade

pituitary was completely desensitised. Alternatively, the GnRHa could have been given in the early follicular phase with resulting supraphysiological oestrogen levels overcoming the pituitary desensitisation. This is the first report of multiple pregnancy occurring following initiation of treatment for endometriosis with a depot GnRHa. This unfortunate complication clearly emphasises the importance of establishing the date of the last menstrual period before commencing GnRHa treatment and underlines the need for contraception if treatment is commenced in the follicular phase. Finally, with reports of pregnancies occurring with luteal phase administration (Martinez e l al. 1988; Isherwood et al. 1990) as with danazol for the treatment of endometriosis, we should ensure that nonhormonal methods of contraception are advised throughout treatment, no matter where in the menstrual cycle the initial dose of GnRHa is given.

The effect of thrombophylaxis on pregnancy outcome in patients with recurrent pregnancy loss associated with factor V Leiden mutation.

Objective To observe the effect of thrombophylaxis on pregnancy in women with a history of unexplained recurrent pregnancy loss also carrying the factor V Leiden mutation.

LYMPHOMA AND LEUKEMIA COMPLICATING PREGNANCY

The hematologic malignancies rarely complicate pregnancy. Pregnancy is not thought to affect the course of either Hodgkins lymphoma, non-Hodgkins lymphoma, or the leukemias. The prognosis worsens only if there is a delay in diagnosis or treatment. Both chemotherapy and radiotherapy have been administered during pregnancy with favorable results.

Decreased incidence of severe ovarian hyperstimulation syndrome in high risk in-vitro fertilization patients receiving intravenous albumin: a prospective study

The administration of human serum albumin has been reported to prevent severe ovarian hyperstimulation syndrome (OHSS) while undergoing ovarian stimulation protocols for in-vitro fertilization (IVF). This prospective, randomized study investigated the effectiveness of a single dose of human serum albumin (20 g) administered i.v. immediately after oocyte retrieval. Women enrolled in the IVF programme were treated with long gonadotrophin-releasing hormone agonist, triptorelin, and an individually-adjusted human menopausal gonadotrophin protocol. The criteria for inclusion in the study were young age, non-obesity, oestradiol concentration > 9200 pmol/l on the day of human chorionic gonadotrophin administration and > 20 follicles > 14 mm diameter as observed by transvaginal sonography. The treatment group (n = 22) received albumin while the control group (n = 18) did not. Patients were followed-up using ultrasound every 3 days. There was a significantly higher number of severe OHSS cases in the control group (n = 4) than in the treatment group (n = 0) (P = 0.035). Where the data base was restricted to patients with an oestradiol concentration > 15,000 pmol/l, the difference between control and treatment groups was highly significant (P = 0.008). These findings support the use of i.v. albumin in preventing severe OHSS during IVF treatment.

Premature luteinization: could it be an early manifestation of low ovarian reserve?

OBJECTIVE To gain insight into the physiologic significance of premature luteinization and to evaluate whether it could be a manifestation of low ovarian reserve. DESIGN Retrospective evaluation. SETTING Reproductive medicine unit. PATIENT(S) Thirty-one consecutively seen women with normal ovulation and unexplained infertility. INTERVENTION(S) Induction of superovulation with hMG coupled with synchronized IUI. A GnRH agonist was not used during the study. MAIN OUTCOME MEASURE(S) Premature luteinization was defined as a progesterone/estradiol ratio of > 1 on the day of hCG administration. Patients were evaluated during their first cycles of hMG treatment and then were divided into those with (study group) and those without (control group) premature luteinization. The ovarian reserve parameters were compared between the two groups. RESULT(S) Nineteen of the 31 patients with unexplained infertility demonstrated premature luteinization. Patient characteristics were similar between the study and control groups. Mean (+/- SD) day 3 FSH levels were 8.2 +/- 3.3 and 6.6 +/- 1.7 mIU/mL in the study and control groups, respectively. Mean (+/- SD) day 3 estradiol levels were significantly higher in the study than in the control group (74 +/- 49 pg/mL vs. 30 +/- 17 pg/mL, respectively). Mean (+/- SD) estradiol levels on the day of hCG administration also differed significantly between the study and control groups (760 +/- 539 pg/mL vs. 1,568 +/- 675 pg/mL, respectively). Likewise, the number of follicles that were > or = 15 mm on the day of hCG administration was significantly lower in the study than in the control group (2.9 +/- 1.5 vs. 4.3 +/- 1.3, respectively). The total dose of hMG and duration of administration were similar in the two groups. The clinical pregnancy rates after four cycles of treatment were 15.8% and 41.7% in the study and control groups, respectively. CONCLUSION(S) This preliminary work suggests that, in cycles that are not treated with a GnRH agonist, signs of premature luteinization in patients with unexplained infertility could be an early manifestation of low ovarian reserve. It appears that hMG treatment in this group of patients could uncover the pathogenesis of their infertility.

Routine thyroid function tests in infertile women: Are they necessary?

To investigate the yield of routine thyroid function testing in infertile women, the records of 444 infertile women were categorized to standard infertility groups. Thyroid function was evaluated by measuring plasma free thyroxine and thyroid-stimulating hormone. All free thyroxine values were in the normal range (0.8 to 1.8 ng/ml), and only three thyroid-stimulating hormone values were higher than the normal range (0.15 to 4.5 mIU/L). The three women had ovulatory dysfunction. Thyroid function testing is more prudent in screening the subset of infertile women with ovulatory dysfunction and not as a routine measure in the infertile population.

A simple multivariate score could predict ovarian reserve, as well as pregnancy rate, in infertile women

OBJECTIVE To find a simple multivariate score that has the potential to predict ovarian reserve, as well as pregnancy rate, in infertile women. DESIGN A prospective study. SETTING A university-affiliated reproductive medicine unit. PATIENT(S) One hundred sixty-eight consecutive women undergoing their first IVF-ET treatment at our unit. INTERVENTION(S) Basal ovarian reserve studies, endocrine and sonographic, were performed before starting therapy. After completion of treatment, a logistic regression analysis was performed to examine which parameters significantly determined low ovarian reserve. These parameters were incorporated thereafter in a multivariate score to predict ovarian reserve, as well as clinical pregnancy rate. MAIN OUTCOME MEASURE(S) Low ovarian reserve defined as <or=3 oocytes on retrieval day and clinical implantation and pregnancy rates. RESULT(S) Logistic regression analysis revealed that age, antral follicle count, basal FSH, FSH/LH ratio, mean ovarian volume, infertility duration, number of previous cycle cancellations, and body mass index were all, in decreasing significance, independent factors that determine low ovarian reserve. The multivariate score was shown to have a distinctive prediction of ovarian reserve. A cumulative score of >14 was shown to be more accurate in predicting low ovarian reserve than age, day 3 FSH, or antral follicle count separately. Moreover, a score of >14 was shown to have a sensitivity of 88% and a specificity of 69% in predicting low ovarian reserve. More important, women with a score of >14 had significantly lower clinical implantation and pregnancy rates relative to women with a score of <or=14, corresponding to 6.7% versus 22.4%, and 11.3% versus 38.6%, respectively. CONCLUSION(S) A novel and simple multivariate score using clinical and basal endocrine and sonographic parameters has a distinctive prediction of low ovarian reserve in infertile women undergoing assisted reproductive technology treatment. Moreover, it has the potential to predict clinical implantation and pregnancy rates in women with low and good ovarian reserve.