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Adolescent infertility—to treat or not to treat
CASE REPORT Adolescent infertility—to treat or not to treat Ronit Haimov-Kochman, M.D., Tal Imbar, M.D., Murshid Farchat, M.D., Yuval Bdolah, M.D., and Arye Hurwitz, M.D. IVF Unit, Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Mt. Scopus, Jerusalem, Israel
Objective: To present the set of reasons for and against fertility treatment for a very young patient. Design: An expert opinion based on clinical experience. Setting: An academic-affiliated fertility clinic situated in East Jerusalem. Patient(s): A 16-year-old married teenager with 2 years’ duration of infertility due to polycystic ovarian syndrome was referred to our infertility center after treatment with six cycles of clomiphene citrate and ovarian drilling. Intervention(s): Counseling of the options of fertility treatments, weight reduction, physical exercise, metformin intake, and an additional gonadotropins–intrauterine insemination cycle with IVF backup. Main Outcome Measure(s): Successful pregnancy while avoiding the risk of ovarian hyperstimulation syndrome. Result(s): The patient conceived a single embryo and on the 30th week of gestation suffered premature uterine contractions and gave birth to a 1,330-g preterm male newborn. Conclusion(s): Adolescent contraception and unintended pregnancies are prevalent issues in the Western world, whereas adolescent infertility is unheard of. Early age of marriage and conception imposes tremendous dilemma to the society of reproductive endocrinologists. This important cultural issue ought to be debated regarding the age at marriage, the age at first pregnancy, and the treatment of infertility in married ‘‘minors’’ who need treatment. Such a debate is likely to encourage development of formal guidelines for practitioners, which would clearly be beneficial. (Fertil Steril 2008;90:2009.e1–e4. 2008 by American Society for Reproductive Medicine.) Key Words: Adolescence, infertility, IVF, treatment
CASE REPORT A.H. was presented to our fertility clinic in East Jerusalem when she was 16 years old, complaining of 2 years of infertility. She had been married to her 23-years-old second cousin. She was generally healthy, and since her menarche she had long periods of amenorrhea. Her height was 1.58 m and weight 71 kg [body mass index (BMI) 28.4 kg/m2]. Her waist/hip ratio was 0.9. Apart from obesity and facial acne, her physical and gynecologic examinations were normal. Her hormonal profile showed FSH 5.5 IU/L, LH 3.8 IU/L, LH/FSH 0.69, total T 4.2 nmol/L [0–3 nmol/L], SHBG 47 [24–180], free androgen index 8.97 [0.02–6], 17hydroxyprogesterone 5.3 nmol/L [0.3–15], PRL 290 mU/L [72–480 mU/L], and TSH 5.54 mU/L [0.35–5.5 mU/L]. The sonographic scan revealed enlarged ovaries with small rosary-like arranged follicles and hyperechoic stroma. A.H. was diagnosed as suffering from polycystic ovarian syndrome (PCOS). Since the age of 14 she was treated with Received February 13, 2008; revised and accepted February 26, 2008. R.H.-K. has nothing to disclose. T.I. has nothing to disclose. M.F. has nothing to disclose. Y.B. has nothing to disclose. A.H. has nothing to disclose. Reprint requests: Ronit Haimov-Kochman, Department of Obstetrics and Gynecology, Hadassah Medical Center, PO Box 24035, Mt. Scopus, Jerusalem 91240, Israel (FAX: þ972 2 581 4210; E-mail: kochman@ hadassah.org.il).
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six cycles of 50–200 mg/day clomiphene citrate (CC), and when proven irresponsive to CC she was treated with gonadotropins (GT) for induction of ovulation and intrauterine inseminations (IUI) for four cycles. At the age of 15 she had laparoscopic ovarian drilling because of a failure to conceive with GT ovulation induction. Overall, when presented to our team at 16 years of age, A.H. already had primary evaluation of infertility, diagnosis of PCOS, and experienced laparoscopic ovarian drilling and ten cycles of ovulation inductions accompanied by IUI. After discussing the optimal approach to this very young patient among our team and counseling with her and her husband of the options of fertility treatments, we suggested weight reduction, physical exercise and 1500 mg/day metformin. The patient was offered an additional GT-IUI cycle under our close supervision with IVF backup if needed. The feeling was that she was too young for an immediate IVF attempt which would obviously be our next option in an older woman. A.H. was treated with rFSH (Gonal F; Serono, Nes Ziona, Israel) and 0.25 mg/day GnRH antagonist (Cetrotide; Serono), because 14-mm follicles were detected. Her E2 level was 10,117 IU and follicular (>17 mm) count was 8, when she was treated with 0.2 mg GnRH analogue (Decapeptyl; Ipsen Pharma Biotech, Signes, France). Twenty-five oocytes were retrieved, and 20 embryos developed after IVF. All of the embryos were cryopreserved to avoid the risk of ovarian
Fertility and Sterility Vol. 90, No. 5, November 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
2009.e1
hyperstimulation syndrome. At the next cycle after endometrial conditioning with 6 mg/day b-estradiol (Estrofem; Novo Nordisk, Bagsverd, Denmark) and vaginal application of 800 mg/day micronized P (Utrogestan; Besins International, CTS, Pathach Tikva, Israel), two embryos were transfered into the uterus. One embryo developed, and on the 30th week of gestation the patient suffered premature uterine contractions and gave birth to a 1,330-g preterm male newborn. DISCUSSION Adolescent contraception and unintended pregnancies are prevalent issues in the Western world, whereas adolescent infertility is unheard of. Early age of marriage and conception imposes tremendous dilemma to the society of reproductive endocrinologists. Here we present the set of reasons for and against fertility treatment for a very young patient. To Treat Cultural attitudes toward age of marriage All over the Western world, female adolescent health topics deal with sexually transmitted disease prevention, contraception, and unintended pregnancies, whereas issues such as adolescent marriage, infertility, and infertility treatments are ignored or overlooked. This trend prevails because the mean age of marriage in the Western world is 10 years older than adolescence [e.g., between 1993–2003 the mean age of marriage in the U.K. ranged 26.2–28.9 years and it is steadily rising (1)]. However, the age of marriage differs dramatically throughout the world. According to UNICEF’s estimates, over 60 million women aged 20–24 years were married/in union before the age of 18 (2). In the Islamic Mediterranean societies (e.g., Egypt, Jordan, and Turkey) the percentage of women married before the age of 20 is 40%-65% (3). Two-thirds of young women in some countries of sub-Saharan Africa marry before age 20 (4). In several of these countries, high proportions of women marry at even younger ages (14–16 years) (5), and the girl may not live with the husband until she is fit for marital sexual relations (6). Cultural attitudes toward child bearing The fertility rate of Muslim women in Israel was one of the highest in the world at the 1970s (9.2). During the 1990s the fertility rate of Muslim women in Israel decreased to 4.7, still higher than Christian Arabs (2.6), Druze (3.1), and Jews (2.7) (7). The mean number of children desired by married women in the 1980s was about 4 in Egypt and Tunisia, 5 in Morocco and Yemen, 6 in Jordan, Syria, and Sudan, and 9 in Mauritania (8). Middle Eastern cultures tend to encourage large families, and, although trends vary among countries, high fertility is common throughout the region. On average, Middle Eastern women give birth to five children by age 45. Women in the Middle East have about three more children than women in developed countries (9). A society with exceedingly high fertility rate (10) imposes strong peer and family pressure on infertile women, especially the young and less-educated ones. 2009.e2
Haimov-Kochman et al.
Cultural and familial attitudes toward woman’s identity and status In parts of Arab society, the fertility of the woman plays a major social role. In 1987, a survey among 8,500 Arab women showed that the great majority wish for a large family (11). The situation may have changed since; however, women who bear more children may still achieve a more stable position in the family and a greater social recognition. Patterns of teenage family formation (i.e., both marriage and childbearing behaviors) tend to be repeated intergenerationally. The intergenerational patterns appear to operate at least in part through the socioeconomic and family context in which the children grow up (12). The adolescent recently married couple is totally dependent on the wider family in terms of income and residence, therefore particularly vulnerable to family scrutinizing and pressure. Adolescent autonomy—the legal aspects In spite the fact that teenagers are considered by Israeli law to be minors, legally incompetent of making independent decisions, in special occasions, such as in cases of termination of an unwanted pregnancy, adolescent consent is fully respected. The dilemma of teenage autonomy has grown further after the issue of the Israeli Basic Law of Human Dignity and Liberty in 1992: ‘‘There shall be no violation of the life, body, or dignity of any person as such. All persons are entitled to protection of their life, body, and dignity. All persons have the right to privacy and to intimacy,’’ Should adolescent privacy and intimacy be protected? With these personal issues, the legal status of adolescent autonomy and liberty for intimacy differs from that of adults and thus generating newly evolving legal controversies. There is no easy answer to the questions of whether teenagers enjoy the spirit of this basic law as adults do, and how much we can ‘‘stretch’’ the validity of this basic law. Regular laws (not basic laws) and bylaws restrict the legal competence to adults, thus excluding teenagers. Paradoxically, a teenage mother, as a parent and a guardian of her child, is authorized to sign an informed consent regarding an operation for her child, while she is not allowed to consent to ovum pick-up or an appendectomy that she may need. This is because no age limits have been set by law for a ‘‘parent’’ whereas age limits have been set for legal competency. Another option is to view the couple as a new legal construction. Then, rather than dealing with an individual, the law deals with a couple, empowering its legal and social competency. Evidently, it is controversial that the parents, commonly authorized to be guardians of their children, decide on nonlife-saving procedures such as infertility treatments. Therefore it may be argued that the decision to embark on infertility therapy is personal and intimate and should be left exclusively for the young couple based on the adolescent’s right to privacy and intimacy. Moreover, legal obstacles preventing adolescent infertility treatment may lead to divorce as well as a search of illegal and unprofessional infertility treatments.
Adolescent infertility—to treat or not
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The right to treatment Legally speaking, there are laws set for the rights of patients rather than the physicians. Physicians may not be allowed to abstain from delivering fertility treatments, whereas a patient’s right for fertility treatment is well established. The availability of fertility technologies in Israel The wide availability and the generous public funding of cutting edge fertility technologies in Israel facilitate the encounter of the infertile woman with the fertility caregiver. The number of IVF centers in Israel is 3.6 per 106 people, more than twice the numbers in the U.K. (1.4) and the U.S. (1.5). The annual number of IVF cycles in Israel is 1,700 per 106 people, about 3–10 times the number of cycles in U.K. (500) and U.S. (150) (13). Not to Treat The adolescent’s right to achieve maturity and education As formal education has become more available in developing countries, it has become a factor in delaying marriage. Women who marry and conceive early tend to drop out of primary education systems (4). Marriage of girls younger than 18 may compromise their development and often results in early pregnancy, with little education and poor vocational training reinforcing the gendered nature of poverty. Young married girls are a unique, often invisible, group. Required to perform heavy amounts of domestic work, under pressure to demonstrate fertility, and responsible for raising children while still children themselves, married girls and child mothers face constrained decision making and reduced life choices (14). Focusing primarily on Benin, Colombia, India, and Turkey, Jenson and Thornton (15) found strong correlations between a woman’s age at marriage and the level of education she achieves as well as the age at which she gives birth to her first child. Evidence shows that the more education a girl receives, the less likely she is to marry and conceive as an adolescent (16). Decreasing the pressure on young women to conceive through education and advocacy about the dangers of early motherhood should be reinforced (14). Adolescent autonomy—the legal aspects According to Israeli law, teenagers until the age of 18 years are considered to be minors, who are incompetent of making independent decisions. Adolescents generally are not authorized to sign informed consent to medical therapies. Should infertility treatments serve as an exception? Infertility therapies may be dangerous to the adolescent’s recent and future health regarding risks such as ovarian hyperstimulation syndrome, multifetal pregnancy, anesthesia, and intraperitoneal hemorrhage during ovum pick-up procedures. Because teenagers are legally incompetent, they cannot consent to an IVF program that is not imperative and may be life threatening. The right to treatment The patient’s right to fertility treatment is well established, but when the patient’s right of childbearing depends on a third party such as a fertility unit or a hospital, the extensiveness of this right is reduced. The autonomy of the patient of any age is not absolute. Because of the need for the physician’s collaboration, the physician’s auFertility and Sterility
tonomy is involved as well. When the medical decision favors avoiding or postponing fertility treatment, it is the obligation of the fertility caregiver to discuss it with the patient and to abstain from providing treatment. The unknown sequelae of controlled ovarian hyperstimulation drugs in adolescence Overall, retrospective cohort and case-control studies do not find clear evidence that ovulation-stimulating drugs used in controlled ovarian hyperstimulation programs and IVF increase the risk of breast, endometrial, and ovarian cancers (17–19). In general, infertile women have higher breast and endometrial cancer risk than the general population (18, 19). Conflicting evidence associates clomiphene to increased risk of both invasive breast and endometrial cancers. The cancer risk of both was amplified in nulliparous clomiphene-treated women, with higher doses leading to higher risk (18–20). The risk of breast cancer may also be increased in women with a positive family history. Because only 8.2% of the cohort were younger than 25 years when treated, the studies could not rule out the possibility that certain subgroups of users, such as very young women, might experience elevation in cancer risk with intake of ovulation-stimulating drugs. Furthermore, in anovulatory infertile adolescents oral contraception should be used as a useful preventive measure for the risk of endometrial cancer. Bad obstetric outcome of adolescent pregnancies Teenage pregnancies have less favorable outcomes. In the Netherlands, 4,500 teenage pregnancies were studied to compare the risk of preterm birth, low birth weight, and delivering a small-for-gestational-age baby between teenagers and older women. Women aged 13–19 years had 1.5 times higher risk of preterm labor than women aged 20–29 years (P<.0001). The risk of intrauterine death was 4 times as high for ages 13–17 years and 2 times as high for ages 18–19 years compared with older women (P<.0001) (21). Even in the Netherlands, with the lowest teenage pregnancy rate in the Western world and a prenatal care system of high quality, teenage pregnancies have less favorable outcomes. It is reasonable to assume that the perinatal outcome in less developed societies may even be worse. CONCLUSIONS On August 2007, a European Society of Human Reproduction and Embryology (ESHRE) Task Force on Ethics and Law 13 report was issued concerning the welfare of the child in medically assisted reproduction (22). The article pointed at the welfare of the conceived child as the focus of concern, whereas the welfare of the mother-child was ignored. Eventually the welfare of both the child and the mother-child should be the physician’s concern as a contributor to the parental project. ‘‘The physician must take into account presently known risk factors for the welfare of the future child [and the would-be mother-child—our addition]. To avoid prejudice, arbitrariness, and discrimination, objective evidence must be sought to be able to offer good reasons for refusing medical assistance.’’ Apart from health reasons that may carry 2009.e3
a potential risk for the welfare of the future child, psychosocial factors may be significant as well; however, the immaturity of the teenage mother has not been mentioned. Could the physician abstain from providing fertility treatment based on his or her judgment of the child and parental welfare? The ESHRE task force suggested two strategies that are applicable to our conflict as well: 1) conditional treatment: the physician may collaborate if the risk to the teenage mother can be diminished, e.g., by postponing treatment to older age; and 2) refusal of treatment due to objection of conscience and referral of the patient to another fertility center. As long as the right of the physician to abstain from providing fertility treatment is not regulated, the role of the physician is reduced to discussing the issues with the young patient and her guardian. Despite our desire to consult, educate, and give sensible arguments for postponing ART treatment, the couple has to decide whether to perform the procedure or not. The decision to embark on infertility therapy should be tailored by the treating team to the specific case. From our experience, it is obvious that as long as there is no law restricting treatment before the age of 18, the majority of these patients will elect to go further and perform ART mostly because of sociocultural reasons. Acknowledgments: The authors are grateful to Ms. Amal Afifi, the devoted coordinator of the Hadassah Mt. Scopus affiliated infertility clinic in East Jerusalem, and to Prof. Amiram Adoni for his advice and comments.
REFERENCES 1. National statistics. Available at: http://www.statistics.gov.uk/STATBASE. Accessed November 25, 2006. 2. UNICEF estimates based on MICS and DHS data (1986–2004). Available at: http://www.chilinfo.org/areas/childmarriage. Accessed November 25, 2006. 3. The INFO project. Population reports. USAID. Available at: http:// www.infoforhealth.org/pr/j41/j41table2.shtml#table5. Accessed November 25, 2006. 4. Bledsoe CH, Cohen B. Social dynamics of adolescent fertility in subSaharan Africa. Washington, DC: National Academy Press, 1993:223.
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5. Singh S, Wulf D. Today’s adolescents, tomorrow’s parents: a portrait of the Americas. New York: Alan Guttmacher Institute, 1990:96. 6. Levy R. The social structure of Islam. Cambridge: University Press, 1969. 7. Keysar A, Sabatello E, Shtarkshall R, Ziegler I, Kupinsky S, Peritz E. Fertility and modernization in the Moslem population in Israel. In: Peritz E, Baras M, eds. Studies in the fertility of Israel. Jerusalem: Institute of Contemporary Jewry, Hebrew University, 1992. 8. Farid S. Fertility and family planning in the Arab region. IPPF Med Bull 1986;20:1–3. 9. Omran AR, Roudi F. The Middle East population puzzle. Popul Bull 1993;48:1–40. 10. The Israel Ministry of Foreign Affairs. Marriages, families, and fertility. Available at: http://www.mfa.gov.il/MFA/Archive/Communiques/1998. Accessed November 25, 2006. 11. Ayad M. Ideal family size in Arab countries. Al Usrah Wa Al Umran Al Bashari 1987;5–6:23–36. 12. Kahn JR, Anderson KE. Intergenerational patterns of teenage fertility. Demography 1992;29:39–57. 13. Collins J. An international survey of health economics of IVF and ICSI. Hum Reprod Update 2003;8:265–77. 14. UNICEF statistics. Child marriage. Available at: http://www.childinfo. org/areas/childmarriage/. Accessed May. 25, 2007. 15. Jenson R, Thornton R. Early female marriage in the developing world. Gend Dev 2003;11:9–19. 16. Al Riyami A, Afifi M. Women empowerment and marital fertility in Oman. J Egypt Public Health Assoc 2003;78:55–72. 17. Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE, et al. Ovarian cancer risk after the use of ovulation-stimulating drugs. Obstet Gynecol 2004;103:1194–203. 18. Brinton LA, Scoccia B, Moghissi KS, Westhoff CL, Althuis MD, Mabie JE, et al. Breast cancer risk associated with ovulation-stimulating drugs. Hum Reprod 2004;19:2005–13. 19. Althuis MD, Moghissi KS, Westhoff CL, Scoccia B, Lamb EJ, Lubin JH, et al. Uterine cancer after use of clomiphene citrate to induce ovulation. Am J Epidemiol 2005;161:607–15. 20. Lerner-Geva L, Keinan-Boker L, Blumstein T, Boyko V, Olmar L, Mashiach S, et al. Infertility, ovulation induction treatments and the incidence of breast cancer—a historical prospective cohort of Israeli women. Breast Cancer Res Treat 2006;100:201–12. 21. Buitendijk SE, van Enk A, Oosterhout R, Ris M. Obstetrical outcome in teenage pregnancies in the Netherlands. Ned Tijdschr Geneeskd 1993;137:2536–40. 22. Pennings G, de Wert G, Shenfield F, Cohen J, Tarlatzis B, Devroey P. ESHRE Task Force on Ethics and Law 13: the welfare of the child in medically assisted reproduction. Hum Reprod 2007;22:2585–8.
Adolescent infertility—to treat or not
Vol. 90, No. 5, November 2008
Objective: To present the set of reasons for and against fertility treatment for a very young patient. Design: An expert opinion based on clinical experience. Setting: An academic-affiliated fertility clinic situated in East Jerusalem. Patient(s): A 16-year-old married teenager with 2 years’ duration of infertility due to polycystic ovarian syndrome was referred to our infertility center after treatment with six cycles of clomiphene citrate and ovarian drilling. Intervention(s): Counseling of the options of fertility treatments, weight reduction, physical exercise, metformin intake, and an additional gonadotropins–intrauterine insemination cycle with IVF backup. Main Outcome Measure(s): Successful pregnancy while avoiding the risk of ovarian hyperstimulation syndrome. Result(s): The patient conceived a single embryo and on the 30th week of gestation suffered premature uterine contractions and gave birth to a 1,330-g preterm male newborn. Conclusion(s): Adolescent contraception and unintended pregnancies are prevalent issues in the Western world, whereas adolescent infertility is unheard of. Early age of marriage and conception imposes tremendous dilemma to the society of reproductive endocrinologists. This important cultural issue ought to be debated regarding the age at marriage, the age at first pregnancy, and the treatment of infertility in married ‘‘minors’’ who need treatment. Such a debate is likely to encourage development of formal guidelines for practitioners, which would clearly be beneficial. (Fertil Steril 2008;90:2009.e1–e4. 2008 by American Society for Reproductive Medicine.) Key Words: Adolescence, infertility, IVF, treatment
CASE REPORT A.H. was presented to our fertility clinic in East Jerusalem when she was 16 years old, complaining of 2 years of infertility. She had been married to her 23-years-old second cousin. She was generally healthy, and since her menarche she had long periods of amenorrhea. Her height was 1.58 m and weight 71 kg [body mass index (BMI) 28.4 kg/m2]. Her waist/hip ratio was 0.9. Apart from obesity and facial acne, her physical and gynecologic examinations were normal. Her hormonal profile showed FSH 5.5 IU/L, LH 3.8 IU/L, LH/FSH 0.69, total T 4.2 nmol/L [0–3 nmol/L], SHBG 47 [24–180], free androgen index 8.97 [0.02–6], 17hydroxyprogesterone 5.3 nmol/L [0.3–15], PRL 290 mU/L [72–480 mU/L], and TSH 5.54 mU/L [0.35–5.5 mU/L]. The sonographic scan revealed enlarged ovaries with small rosary-like arranged follicles and hyperechoic stroma. A.H. was diagnosed as suffering from polycystic ovarian syndrome (PCOS). Since the age of 14 she was treated with Received February 13, 2008; revised and accepted February 26, 2008. R.H.-K. has nothing to disclose. T.I. has nothing to disclose. M.F. has nothing to disclose. Y.B. has nothing to disclose. A.H. has nothing to disclose. Reprint requests: Ronit Haimov-Kochman, Department of Obstetrics and Gynecology, Hadassah Medical Center, PO Box 24035, Mt. Scopus, Jerusalem 91240, Israel (FAX: þ972 2 581 4210; E-mail: kochman@ hadassah.org.il).
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six cycles of 50–200 mg/day clomiphene citrate (CC), and when proven irresponsive to CC she was treated with gonadotropins (GT) for induction of ovulation and intrauterine inseminations (IUI) for four cycles. At the age of 15 she had laparoscopic ovarian drilling because of a failure to conceive with GT ovulation induction. Overall, when presented to our team at 16 years of age, A.H. already had primary evaluation of infertility, diagnosis of PCOS, and experienced laparoscopic ovarian drilling and ten cycles of ovulation inductions accompanied by IUI. After discussing the optimal approach to this very young patient among our team and counseling with her and her husband of the options of fertility treatments, we suggested weight reduction, physical exercise and 1500 mg/day metformin. The patient was offered an additional GT-IUI cycle under our close supervision with IVF backup if needed. The feeling was that she was too young for an immediate IVF attempt which would obviously be our next option in an older woman. A.H. was treated with rFSH (Gonal F; Serono, Nes Ziona, Israel) and 0.25 mg/day GnRH antagonist (Cetrotide; Serono), because 14-mm follicles were detected. Her E2 level was 10,117 IU and follicular (>17 mm) count was 8, when she was treated with 0.2 mg GnRH analogue (Decapeptyl; Ipsen Pharma Biotech, Signes, France). Twenty-five oocytes were retrieved, and 20 embryos developed after IVF. All of the embryos were cryopreserved to avoid the risk of ovarian
Fertility and Sterility Vol. 90, No. 5, November 2008 Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
2009.e1
hyperstimulation syndrome. At the next cycle after endometrial conditioning with 6 mg/day b-estradiol (Estrofem; Novo Nordisk, Bagsverd, Denmark) and vaginal application of 800 mg/day micronized P (Utrogestan; Besins International, CTS, Pathach Tikva, Israel), two embryos were transfered into the uterus. One embryo developed, and on the 30th week of gestation the patient suffered premature uterine contractions and gave birth to a 1,330-g preterm male newborn. DISCUSSION Adolescent contraception and unintended pregnancies are prevalent issues in the Western world, whereas adolescent infertility is unheard of. Early age of marriage and conception imposes tremendous dilemma to the society of reproductive endocrinologists. Here we present the set of reasons for and against fertility treatment for a very young patient. To Treat Cultural attitudes toward age of marriage All over the Western world, female adolescent health topics deal with sexually transmitted disease prevention, contraception, and unintended pregnancies, whereas issues such as adolescent marriage, infertility, and infertility treatments are ignored or overlooked. This trend prevails because the mean age of marriage in the Western world is 10 years older than adolescence [e.g., between 1993–2003 the mean age of marriage in the U.K. ranged 26.2–28.9 years and it is steadily rising (1)]. However, the age of marriage differs dramatically throughout the world. According to UNICEF’s estimates, over 60 million women aged 20–24 years were married/in union before the age of 18 (2). In the Islamic Mediterranean societies (e.g., Egypt, Jordan, and Turkey) the percentage of women married before the age of 20 is 40%-65% (3). Two-thirds of young women in some countries of sub-Saharan Africa marry before age 20 (4). In several of these countries, high proportions of women marry at even younger ages (14–16 years) (5), and the girl may not live with the husband until she is fit for marital sexual relations (6). Cultural attitudes toward child bearing The fertility rate of Muslim women in Israel was one of the highest in the world at the 1970s (9.2). During the 1990s the fertility rate of Muslim women in Israel decreased to 4.7, still higher than Christian Arabs (2.6), Druze (3.1), and Jews (2.7) (7). The mean number of children desired by married women in the 1980s was about 4 in Egypt and Tunisia, 5 in Morocco and Yemen, 6 in Jordan, Syria, and Sudan, and 9 in Mauritania (8). Middle Eastern cultures tend to encourage large families, and, although trends vary among countries, high fertility is common throughout the region. On average, Middle Eastern women give birth to five children by age 45. Women in the Middle East have about three more children than women in developed countries (9). A society with exceedingly high fertility rate (10) imposes strong peer and family pressure on infertile women, especially the young and less-educated ones. 2009.e2
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Cultural and familial attitudes toward woman’s identity and status In parts of Arab society, the fertility of the woman plays a major social role. In 1987, a survey among 8,500 Arab women showed that the great majority wish for a large family (11). The situation may have changed since; however, women who bear more children may still achieve a more stable position in the family and a greater social recognition. Patterns of teenage family formation (i.e., both marriage and childbearing behaviors) tend to be repeated intergenerationally. The intergenerational patterns appear to operate at least in part through the socioeconomic and family context in which the children grow up (12). The adolescent recently married couple is totally dependent on the wider family in terms of income and residence, therefore particularly vulnerable to family scrutinizing and pressure. Adolescent autonomy—the legal aspects In spite the fact that teenagers are considered by Israeli law to be minors, legally incompetent of making independent decisions, in special occasions, such as in cases of termination of an unwanted pregnancy, adolescent consent is fully respected. The dilemma of teenage autonomy has grown further after the issue of the Israeli Basic Law of Human Dignity and Liberty in 1992: ‘‘There shall be no violation of the life, body, or dignity of any person as such. All persons are entitled to protection of their life, body, and dignity. All persons have the right to privacy and to intimacy,’’ Should adolescent privacy and intimacy be protected? With these personal issues, the legal status of adolescent autonomy and liberty for intimacy differs from that of adults and thus generating newly evolving legal controversies. There is no easy answer to the questions of whether teenagers enjoy the spirit of this basic law as adults do, and how much we can ‘‘stretch’’ the validity of this basic law. Regular laws (not basic laws) and bylaws restrict the legal competence to adults, thus excluding teenagers. Paradoxically, a teenage mother, as a parent and a guardian of her child, is authorized to sign an informed consent regarding an operation for her child, while she is not allowed to consent to ovum pick-up or an appendectomy that she may need. This is because no age limits have been set by law for a ‘‘parent’’ whereas age limits have been set for legal competency. Another option is to view the couple as a new legal construction. Then, rather than dealing with an individual, the law deals with a couple, empowering its legal and social competency. Evidently, it is controversial that the parents, commonly authorized to be guardians of their children, decide on nonlife-saving procedures such as infertility treatments. Therefore it may be argued that the decision to embark on infertility therapy is personal and intimate and should be left exclusively for the young couple based on the adolescent’s right to privacy and intimacy. Moreover, legal obstacles preventing adolescent infertility treatment may lead to divorce as well as a search of illegal and unprofessional infertility treatments.
Adolescent infertility—to treat or not
Vol. 90, No. 5, November 2008
The right to treatment Legally speaking, there are laws set for the rights of patients rather than the physicians. Physicians may not be allowed to abstain from delivering fertility treatments, whereas a patient’s right for fertility treatment is well established. The availability of fertility technologies in Israel The wide availability and the generous public funding of cutting edge fertility technologies in Israel facilitate the encounter of the infertile woman with the fertility caregiver. The number of IVF centers in Israel is 3.6 per 106 people, more than twice the numbers in the U.K. (1.4) and the U.S. (1.5). The annual number of IVF cycles in Israel is 1,700 per 106 people, about 3–10 times the number of cycles in U.K. (500) and U.S. (150) (13). Not to Treat The adolescent’s right to achieve maturity and education As formal education has become more available in developing countries, it has become a factor in delaying marriage. Women who marry and conceive early tend to drop out of primary education systems (4). Marriage of girls younger than 18 may compromise their development and often results in early pregnancy, with little education and poor vocational training reinforcing the gendered nature of poverty. Young married girls are a unique, often invisible, group. Required to perform heavy amounts of domestic work, under pressure to demonstrate fertility, and responsible for raising children while still children themselves, married girls and child mothers face constrained decision making and reduced life choices (14). Focusing primarily on Benin, Colombia, India, and Turkey, Jenson and Thornton (15) found strong correlations between a woman’s age at marriage and the level of education she achieves as well as the age at which she gives birth to her first child. Evidence shows that the more education a girl receives, the less likely she is to marry and conceive as an adolescent (16). Decreasing the pressure on young women to conceive through education and advocacy about the dangers of early motherhood should be reinforced (14). Adolescent autonomy—the legal aspects According to Israeli law, teenagers until the age of 18 years are considered to be minors, who are incompetent of making independent decisions. Adolescents generally are not authorized to sign informed consent to medical therapies. Should infertility treatments serve as an exception? Infertility therapies may be dangerous to the adolescent’s recent and future health regarding risks such as ovarian hyperstimulation syndrome, multifetal pregnancy, anesthesia, and intraperitoneal hemorrhage during ovum pick-up procedures. Because teenagers are legally incompetent, they cannot consent to an IVF program that is not imperative and may be life threatening. The right to treatment The patient’s right to fertility treatment is well established, but when the patient’s right of childbearing depends on a third party such as a fertility unit or a hospital, the extensiveness of this right is reduced. The autonomy of the patient of any age is not absolute. Because of the need for the physician’s collaboration, the physician’s auFertility and Sterility
tonomy is involved as well. When the medical decision favors avoiding or postponing fertility treatment, it is the obligation of the fertility caregiver to discuss it with the patient and to abstain from providing treatment. The unknown sequelae of controlled ovarian hyperstimulation drugs in adolescence Overall, retrospective cohort and case-control studies do not find clear evidence that ovulation-stimulating drugs used in controlled ovarian hyperstimulation programs and IVF increase the risk of breast, endometrial, and ovarian cancers (17–19). In general, infertile women have higher breast and endometrial cancer risk than the general population (18, 19). Conflicting evidence associates clomiphene to increased risk of both invasive breast and endometrial cancers. The cancer risk of both was amplified in nulliparous clomiphene-treated women, with higher doses leading to higher risk (18–20). The risk of breast cancer may also be increased in women with a positive family history. Because only 8.2% of the cohort were younger than 25 years when treated, the studies could not rule out the possibility that certain subgroups of users, such as very young women, might experience elevation in cancer risk with intake of ovulation-stimulating drugs. Furthermore, in anovulatory infertile adolescents oral contraception should be used as a useful preventive measure for the risk of endometrial cancer. Bad obstetric outcome of adolescent pregnancies Teenage pregnancies have less favorable outcomes. In the Netherlands, 4,500 teenage pregnancies were studied to compare the risk of preterm birth, low birth weight, and delivering a small-for-gestational-age baby between teenagers and older women. Women aged 13–19 years had 1.5 times higher risk of preterm labor than women aged 20–29 years (P<.0001). The risk of intrauterine death was 4 times as high for ages 13–17 years and 2 times as high for ages 18–19 years compared with older women (P<.0001) (21). Even in the Netherlands, with the lowest teenage pregnancy rate in the Western world and a prenatal care system of high quality, teenage pregnancies have less favorable outcomes. It is reasonable to assume that the perinatal outcome in less developed societies may even be worse. CONCLUSIONS On August 2007, a European Society of Human Reproduction and Embryology (ESHRE) Task Force on Ethics and Law 13 report was issued concerning the welfare of the child in medically assisted reproduction (22). The article pointed at the welfare of the conceived child as the focus of concern, whereas the welfare of the mother-child was ignored. Eventually the welfare of both the child and the mother-child should be the physician’s concern as a contributor to the parental project. ‘‘The physician must take into account presently known risk factors for the welfare of the future child [and the would-be mother-child—our addition]. To avoid prejudice, arbitrariness, and discrimination, objective evidence must be sought to be able to offer good reasons for refusing medical assistance.’’ Apart from health reasons that may carry 2009.e3
a potential risk for the welfare of the future child, psychosocial factors may be significant as well; however, the immaturity of the teenage mother has not been mentioned. Could the physician abstain from providing fertility treatment based on his or her judgment of the child and parental welfare? The ESHRE task force suggested two strategies that are applicable to our conflict as well: 1) conditional treatment: the physician may collaborate if the risk to the teenage mother can be diminished, e.g., by postponing treatment to older age; and 2) refusal of treatment due to objection of conscience and referral of the patient to another fertility center. As long as the right of the physician to abstain from providing fertility treatment is not regulated, the role of the physician is reduced to discussing the issues with the young patient and her guardian. Despite our desire to consult, educate, and give sensible arguments for postponing ART treatment, the couple has to decide whether to perform the procedure or not. The decision to embark on infertility therapy should be tailored by the treating team to the specific case. From our experience, it is obvious that as long as there is no law restricting treatment before the age of 18, the majority of these patients will elect to go further and perform ART mostly because of sociocultural reasons. Acknowledgments: The authors are grateful to Ms. Amal Afifi, the devoted coordinator of the Hadassah Mt. Scopus affiliated infertility clinic in East Jerusalem, and to Prof. Amiram Adoni for his advice and comments.
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Adolescent infertility—to treat or not
Vol. 90, No. 5, November 2008