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Premature ovarian failure-the prognostic application of autoimmunity on conception after ovulation induction
Citations from the Literature
distinct effects occurring in subgroups 3 and 5. Highly elevated T and free T levels were observed in subgroup 5 and in overweight patients (subgroup 6). Estrone (Et) serum concentrations were highest in those subgroups (3 and 5) in which acceleration of LH pulse frequency and increments in LH pulse amplitude were most pronounced; these parameters correlated significantly with Et levels. Conclusions: Changes in pulsatile LH release in patients with hyperandrogenemic chronic anovulation correlate primarily with elevated Et levels, rather than with T or A serum concentrations.
Premature ovarian failure-The prognostic application of sutoimmunity on conception after ovulation induction Blumenfeld Z.; Halachmi S.; Peretz B.A.; Shmuel Z.; Golan D.; Makler A.; Brandes J.M. ISR FERTJL STERIL 1993 5914 (750-755) Objective: To assess whether the presence of autoimmune activity in patients with premature ovarian failure (POF) can predict the response to ovulation induction and conception. Design: Assessment of autoimmune activity in patients with POF, correlating the response to ovulation induction with this autoreactivity. Setting: Tertiary care academic center. Patients: Forty women with POF, I5 of them treated by ovulation induction because of infertility. Interventions: All patients were tested for the presence of autoimmune activity, antibodies against various tissues, and I5 of them were treated with combinations of hMG/hCG, glucocorticosteroids as immunosuppressant, and some of them also with a long-acting GnRH agonist. Those patients not interested in infertility were put on hormone replacement therapy (HRT). Main Outcome Measures: Serum E2 and P were measured during ovulation induction as well as folhcular diameter monitoring by transvaginal sonography. Achievement of gestations and their outcome were monitored in the group in which ovulation induction was accomplished. Results: Antibodies against thyroglobulin, nuclear antigens, heart, tissue gluten, or increased levels of immunoglobulin (Ig)M, or decreased levels of complement C, and C4 were significantly different in the patients with POF than in the control population. Autoreactivity of at least one class of the tested antibodies was found in 31 of 40 patients (77%). In I5 patients with autoimmune activity who have undergone ovulation induction using hMG/hCG. I4 pregnancies were achieved in 8 patients. Two of the pregnancies were spontaneous, and I2 were generated by hMG/hCG and fluocortolone, with or without pretreatment with GnRH-a. Twelve healthy babies were generated by IO gestations, 3 ended in spontaneous abortions (23X1), and I is ongoing. All the nonspontaneous pregnancies were achieved in the first three cycles of ovulation induction. Conclusions: Patients with POF and autoimmune activity, suggesting an autoimmune etiology to the ovarian failure, may respond to ovulation induction and have a conception rate of approximately 40”/~ in three cycles. Those who do not conceive in three treatment cycles have a very low probability to conceive; therefore, further attempts of ovulation induction should be discouraged. However, some patients may spontaneously conceive in association with HRT.
95
Induction of follicular growth using recombinant human folliclestimulating hormone in two volunteer women with hypogonadotropic hypogonadism Shoham Z.; Mannaerts B.; lnsler V.; Coelingh-Bennink H. ISR FERTIL STERIL 1993 5914 (738-742) Objective: To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism. Design: An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days. I50 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E, was > 1,100 pmolil and/or one or more growing follicle > I4 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. Setting: Specialist Reproductive Endocrinology and Infertility Unit. Volunteers: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore. Main Outcome Measures: Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology. blood biochemistry, and antirecombinant FSH antibodies. Results: Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, I7 mm), whereas serum A concentrations were very low, and serum Ez concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted. Conclusion: This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E, indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.
PREGNANCY
AND DELIVERY
Changes in platelet intracellular free calcium in normal pregnancy Kilby M.D.; Broughton Pipkin F.; Symonds E.M. GBR BR J OBSTET GYNAECOL 1993 lOtI/4 (375-379) Objective - To determine if platelet intracellular free calcium concentration (p.(Ca*‘)i) changes with gestation in normotensive, uncomplicated pregnancy. Design ~ A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulhparous nonpregnant volunteers. Setting - The antenatal clinic at University Hospital, Queen’s Medical Centre, Nottingham. Subjects - Two groups of women were studied. Thirty-one nulliparous. nonpregnant women not using oral contraception were investigated
Inr J Grnrcol
Ohste~ 44
distinct effects occurring in subgroups 3 and 5. Highly elevated T and free T levels were observed in subgroup 5 and in overweight patients (subgroup 6). Estrone (Et) serum concentrations were highest in those subgroups (3 and 5) in which acceleration of LH pulse frequency and increments in LH pulse amplitude were most pronounced; these parameters correlated significantly with Et levels. Conclusions: Changes in pulsatile LH release in patients with hyperandrogenemic chronic anovulation correlate primarily with elevated Et levels, rather than with T or A serum concentrations.
Premature ovarian failure-The prognostic application of sutoimmunity on conception after ovulation induction Blumenfeld Z.; Halachmi S.; Peretz B.A.; Shmuel Z.; Golan D.; Makler A.; Brandes J.M. ISR FERTJL STERIL 1993 5914 (750-755) Objective: To assess whether the presence of autoimmune activity in patients with premature ovarian failure (POF) can predict the response to ovulation induction and conception. Design: Assessment of autoimmune activity in patients with POF, correlating the response to ovulation induction with this autoreactivity. Setting: Tertiary care academic center. Patients: Forty women with POF, I5 of them treated by ovulation induction because of infertility. Interventions: All patients were tested for the presence of autoimmune activity, antibodies against various tissues, and I5 of them were treated with combinations of hMG/hCG, glucocorticosteroids as immunosuppressant, and some of them also with a long-acting GnRH agonist. Those patients not interested in infertility were put on hormone replacement therapy (HRT). Main Outcome Measures: Serum E2 and P were measured during ovulation induction as well as folhcular diameter monitoring by transvaginal sonography. Achievement of gestations and their outcome were monitored in the group in which ovulation induction was accomplished. Results: Antibodies against thyroglobulin, nuclear antigens, heart, tissue gluten, or increased levels of immunoglobulin (Ig)M, or decreased levels of complement C, and C4 were significantly different in the patients with POF than in the control population. Autoreactivity of at least one class of the tested antibodies was found in 31 of 40 patients (77%). In I5 patients with autoimmune activity who have undergone ovulation induction using hMG/hCG. I4 pregnancies were achieved in 8 patients. Two of the pregnancies were spontaneous, and I2 were generated by hMG/hCG and fluocortolone, with or without pretreatment with GnRH-a. Twelve healthy babies were generated by IO gestations, 3 ended in spontaneous abortions (23X1), and I is ongoing. All the nonspontaneous pregnancies were achieved in the first three cycles of ovulation induction. Conclusions: Patients with POF and autoimmune activity, suggesting an autoimmune etiology to the ovarian failure, may respond to ovulation induction and have a conception rate of approximately 40”/~ in three cycles. Those who do not conceive in three treatment cycles have a very low probability to conceive; therefore, further attempts of ovulation induction should be discouraged. However, some patients may spontaneously conceive in association with HRT.
95
Induction of follicular growth using recombinant human folliclestimulating hormone in two volunteer women with hypogonadotropic hypogonadism Shoham Z.; Mannaerts B.; lnsler V.; Coelingh-Bennink H. ISR FERTIL STERIL 1993 5914 (738-742) Objective: To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism. Design: An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days. I50 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E, was > 1,100 pmolil and/or one or more growing follicle > I4 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. Setting: Specialist Reproductive Endocrinology and Infertility Unit. Volunteers: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore. Main Outcome Measures: Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology. blood biochemistry, and antirecombinant FSH antibodies. Results: Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, I7 mm), whereas serum A concentrations were very low, and serum Ez concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted. Conclusion: This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E, indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.
PREGNANCY
AND DELIVERY
Changes in platelet intracellular free calcium in normal pregnancy Kilby M.D.; Broughton Pipkin F.; Symonds E.M. GBR BR J OBSTET GYNAECOL 1993 lOtI/4 (375-379) Objective - To determine if platelet intracellular free calcium concentration (p.(Ca*‘)i) changes with gestation in normotensive, uncomplicated pregnancy. Design ~ A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulhparous nonpregnant volunteers. Setting - The antenatal clinic at University Hospital, Queen’s Medical Centre, Nottingham. Subjects - Two groups of women were studied. Thirty-one nulliparous. nonpregnant women not using oral contraception were investigated
Inr J Grnrcol
Ohste~ 44