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Routine thyroid function tests in infertile women: Are they necessary?
Volume 171, Number 5 Am J Obstet Gynecol
Shalav at al.
Krauer F. Longitudinal study of carcinoembryonic antigen and cancer antigen CA 125 in ovarian cancer. Gynecol Dncol 1985;21:1-6. 22. Atack DB, Nisker JA, Allen HH, Tustanoff ER, Levin L. CA 125 surveillance and second-look laparotomy in ovarian carcinoma. A\lJ DBSTEr GYNECOL 1986;154:287-9. 23. Schwartz PE, Chambers SK, Chambers JT, Gutmann J, Katopodis N, Foemmal R. Circulating tumor markers in the monitoring of gynecologic malignancies. Cancer 1987; 60:353-61.
24. Einhorn N, Knapp RC, Bast RC Jr, Zurawski VR Jr. CA 125 assay used in corti unction with CA 15-3 and TAG-72 assays for discrimination between malignant and nonmalignant diseases of the ovary. Acta Dncol 1989;28: 655-7. 25. Bast RC Jr, Knauf S, Epenetos A, et al. Coordinate elevation of serum markers in ovarian cancer but not in benign disease. Cancer 1991;68:1758-63.
Routine thyroid function tests in infertile women: Are they necessary? Eliezer Shalev, MD, Shlomo Eliyahu, MD, M. Ziv, MD, and Moshe Ben-Ami, MD Afola, Israel 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. (AM J OSSTET GVNECOL 1994;171 :1191-2.)
Key words: Infertile women, thyroid function testing, ovulatory dysfunction The low incidence of hypothyroidism in the pregnant patient is related to the close association between infertility and hypothyroidism. 1 Patients with hypothyroidism can have either primary or secondary amenorrhea but may be in a compensated state with normal thyrox'ine (T4) levels achieved by increased thyroid-stimulating hormone (TSH) secretion. Because the treatment for hypothyroidism is simple, many infertility clinics commonly screen infertile women for thyroid function. We investigated the yield of routine thyroid function testing in our outpatient infertility clinic.
Material and methods We reviewed the records of 444 women of infertile couples enrolled in our outpatient infertility clinic during a 3-year period (January 1989 through June 1992) and categorized them into infertility subgroups atcording to standard clinical criteria. Thyroid function was From the Department of Obstetrics and Gynecology, Central Emek Hospital. ReceIVed for publicatzon Apnl 18, 1994; accepted June 2, 1994. Reprznt requests: E. Shalev, MD, Department of Obstetrics and Gynecology, Central Emek Hosp!tal, Afida, 18101, Israel. Copynght © 1994 by Mo:,by-Year Book, Inc.
0002-9378/94 $3.00 + 0
6!l158161
evaluated by measuring plasma free T 4 and thyroid function (TSH) at the early proliferative phase (days 2 to 5 of the cycle). The kit we used for those measurements is Amerlite (Kodak Clinical Diagnostics, Ltd., Amersham, United Kingdom).
Results Free T 4 was measured in 359 women and TSH in 444 women. All free T4 results were normal (0.8 to 1.8 ng/ml), and only three TSH values (0.7%) were abnormal: 10.03, 8.9, and 5.3 mIU/L (normal range 0.15 to 4.5 mIU/L). Two women had clinical signs and symptoms of hypothyroidism. The third had slightly elevated TSH levels (5.3 mIU/L) with normal free T4 levels; she was asymptomatic and did not have any signs of hypothyroidism. All three women were assigned to the ovulatory dysfunction group. Comment Disorders of the menstrual cycle, usually menometrorrhagia, but occasionally even amenorrhea, are common in hypothyroidism, and many of the cycles seem to be anovulatory. Often the midcycle gonadotropin surge is absent and progesterone levels remain low throughout the cycle. Estrogen levels are relatively low and constant. 2 1191
1192
Shalev et al.
The reported hormonal changes include reduction in sex hormone binding globulin, an increase in estradiol metabolic clearance, an increased production of estriol at the expense of estrone, and enhancement of conversion of androstenedione to testosterone." Obviously the high frequency of anovulation reduces the pregnancy rate in hypothyroid women. Another mechanism of fertility disturbance in hypothyroid women is through elevated TSH, which causes an elevation of prolactin. Increased levels of prolactin cause a woman to progress through a spectrum of ovulatory dysfunction problems (e.g., luteal-phase insufficiency, anovulation, and amenorrhea). In our study the incidence of subclinical hypothyroidism in all 444 infertile women was 0.23% (one in 444), but in the subgroup of women with ovulatory dysfunction (114 women) the incidence amounted to 0.88%. Our findings suggest a low yield of routine thy-
November 1994 Am J Obstet Gynecol
roid function tests in all infertile women. Our results, and those of others, 4 indicate that subclinical hypothyroidism is of greater importance in women with ovulatory dysfunction, and it is conceivably more prudent to screen for subclinical hypothyroidism only in that subset of infertile women. REFERENCES 1. Potter JD. Hypothyroidism and reproductive failure. Surg GynecolObstet 1980;150:251-5. 2. Akande EO. Plasma concentration of gonadotropins, estrogen and progesterone in hypothyroid women. Br J Obstet Gynaecol 1975;82:552-6. 3. Gordon GG, Southren AL, Tochimoto S, Rand JJ, Olivo J. Effect of hyperthyroidism and hypothyroidism on the metabolism of testosterone and androstenediones in man. J Clin Endocrinol Metab 1969;29:164-7. 4. Strickland DM, Whitted WA. Screening infertile women for subclinical hypothyroidism [Letter]. AM J OBSTET GYNECOL 1990; 163:262-3.
Availability of JOURNAL Back Issues As a service to our subscribers, copies of back issues of the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY for the preceding 5 years are maintained and are available for purchase from the Publisher, Mosby-Year Book, Inc., at a cost of $10.50 per issue. The following quantity discounts are available: one fourth off on quantities of 12 to 23 and one third off on quantities of 24 or more. Please write to Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Drive, St. Louis, MO 63146-3318 or call (800) 453-4351 or (314) 453-4351 for information on availability of particular issues. If back issues are unavailable from the Publisher, photocopies of complete issues are available from University Microfilms International, 300 N. Zeeb Road, Ann Arbor, MI 48106. Tel.: (313) 761-4700.
Shalav at al.
Krauer F. Longitudinal study of carcinoembryonic antigen and cancer antigen CA 125 in ovarian cancer. Gynecol Dncol 1985;21:1-6. 22. Atack DB, Nisker JA, Allen HH, Tustanoff ER, Levin L. CA 125 surveillance and second-look laparotomy in ovarian carcinoma. A\lJ DBSTEr GYNECOL 1986;154:287-9. 23. Schwartz PE, Chambers SK, Chambers JT, Gutmann J, Katopodis N, Foemmal R. Circulating tumor markers in the monitoring of gynecologic malignancies. Cancer 1987; 60:353-61.
24. Einhorn N, Knapp RC, Bast RC Jr, Zurawski VR Jr. CA 125 assay used in corti unction with CA 15-3 and TAG-72 assays for discrimination between malignant and nonmalignant diseases of the ovary. Acta Dncol 1989;28: 655-7. 25. Bast RC Jr, Knauf S, Epenetos A, et al. Coordinate elevation of serum markers in ovarian cancer but not in benign disease. Cancer 1991;68:1758-63.
Routine thyroid function tests in infertile women: Are they necessary? Eliezer Shalev, MD, Shlomo Eliyahu, MD, M. Ziv, MD, and Moshe Ben-Ami, MD Afola, Israel 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. (AM J OSSTET GVNECOL 1994;171 :1191-2.)
Key words: Infertile women, thyroid function testing, ovulatory dysfunction The low incidence of hypothyroidism in the pregnant patient is related to the close association between infertility and hypothyroidism. 1 Patients with hypothyroidism can have either primary or secondary amenorrhea but may be in a compensated state with normal thyrox'ine (T4) levels achieved by increased thyroid-stimulating hormone (TSH) secretion. Because the treatment for hypothyroidism is simple, many infertility clinics commonly screen infertile women for thyroid function. We investigated the yield of routine thyroid function testing in our outpatient infertility clinic.
Material and methods We reviewed the records of 444 women of infertile couples enrolled in our outpatient infertility clinic during a 3-year period (January 1989 through June 1992) and categorized them into infertility subgroups atcording to standard clinical criteria. Thyroid function was From the Department of Obstetrics and Gynecology, Central Emek Hospital. ReceIVed for publicatzon Apnl 18, 1994; accepted June 2, 1994. Reprznt requests: E. Shalev, MD, Department of Obstetrics and Gynecology, Central Emek Hosp!tal, Afida, 18101, Israel. Copynght © 1994 by Mo:,by-Year Book, Inc.
0002-9378/94 $3.00 + 0
6!l158161
evaluated by measuring plasma free T 4 and thyroid function (TSH) at the early proliferative phase (days 2 to 5 of the cycle). The kit we used for those measurements is Amerlite (Kodak Clinical Diagnostics, Ltd., Amersham, United Kingdom).
Results Free T 4 was measured in 359 women and TSH in 444 women. All free T4 results were normal (0.8 to 1.8 ng/ml), and only three TSH values (0.7%) were abnormal: 10.03, 8.9, and 5.3 mIU/L (normal range 0.15 to 4.5 mIU/L). Two women had clinical signs and symptoms of hypothyroidism. The third had slightly elevated TSH levels (5.3 mIU/L) with normal free T4 levels; she was asymptomatic and did not have any signs of hypothyroidism. All three women were assigned to the ovulatory dysfunction group. Comment Disorders of the menstrual cycle, usually menometrorrhagia, but occasionally even amenorrhea, are common in hypothyroidism, and many of the cycles seem to be anovulatory. Often the midcycle gonadotropin surge is absent and progesterone levels remain low throughout the cycle. Estrogen levels are relatively low and constant. 2 1191
1192
Shalev et al.
The reported hormonal changes include reduction in sex hormone binding globulin, an increase in estradiol metabolic clearance, an increased production of estriol at the expense of estrone, and enhancement of conversion of androstenedione to testosterone." Obviously the high frequency of anovulation reduces the pregnancy rate in hypothyroid women. Another mechanism of fertility disturbance in hypothyroid women is through elevated TSH, which causes an elevation of prolactin. Increased levels of prolactin cause a woman to progress through a spectrum of ovulatory dysfunction problems (e.g., luteal-phase insufficiency, anovulation, and amenorrhea). In our study the incidence of subclinical hypothyroidism in all 444 infertile women was 0.23% (one in 444), but in the subgroup of women with ovulatory dysfunction (114 women) the incidence amounted to 0.88%. Our findings suggest a low yield of routine thy-
November 1994 Am J Obstet Gynecol
roid function tests in all infertile women. Our results, and those of others, 4 indicate that subclinical hypothyroidism is of greater importance in women with ovulatory dysfunction, and it is conceivably more prudent to screen for subclinical hypothyroidism only in that subset of infertile women. REFERENCES 1. Potter JD. Hypothyroidism and reproductive failure. Surg GynecolObstet 1980;150:251-5. 2. Akande EO. Plasma concentration of gonadotropins, estrogen and progesterone in hypothyroid women. Br J Obstet Gynaecol 1975;82:552-6. 3. Gordon GG, Southren AL, Tochimoto S, Rand JJ, Olivo J. Effect of hyperthyroidism and hypothyroidism on the metabolism of testosterone and androstenediones in man. J Clin Endocrinol Metab 1969;29:164-7. 4. Strickland DM, Whitted WA. Screening infertile women for subclinical hypothyroidism [Letter]. AM J OBSTET GYNECOL 1990; 163:262-3.
Availability of JOURNAL Back Issues As a service to our subscribers, copies of back issues of the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY for the preceding 5 years are maintained and are available for purchase from the Publisher, Mosby-Year Book, Inc., at a cost of $10.50 per issue. The following quantity discounts are available: one fourth off on quantities of 12 to 23 and one third off on quantities of 24 or more. Please write to Mosby-Year Book, Inc., Subscription Services, 11830 Westline Industrial Drive, St. Louis, MO 63146-3318 or call (800) 453-4351 or (314) 453-4351 for information on availability of particular issues. If back issues are unavailable from the Publisher, photocopies of complete issues are available from University Microfilms International, 300 N. Zeeb Road, Ann Arbor, MI 48106. Tel.: (313) 761-4700.