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Controversies in gender selection
International Congress Series 1271 (2004) 345 – 348
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Controversies in gender selection Zaid Kilani * The Farah Hospital, May Ziadeh Street, P.O. Box 5323, Jabal Amman, 4th Circle, Amman 11183, Jordan
Abstract. Introduction: The issue of gender determination is an old one. It was practiced in a way or another all through ages. The traditional option available for couples is to keep trying in the hope of achieving their goal. Different options include sperm separation and selective termination of pregnancy. Preimplantation genetic diagnosis (PGD) offered an accurate method which guarantees the transfer of the wanted gender. The application of PGD for that purpose had been the subject of heated debate and complex ethical arguments. We will extend and express some views based upon practical experience regarding the application of PGD for gender selection. Methods: After approval of the hospital ethical committee, 495 IVF-ICSI cycles were initiated over 4 years of experience. In 490 cycles couples had at least three daughters and wished to have a son. Out of 2445 embryos obtained, 2216 (90.6%) embryos were biopsied on day 3 and analyzed using fluorescent in situ hybridization (FISH) for X,Y. Chromosomes 13,16,18,21 were included upon request. Results: Out of the 2216 embryos analyzed, 845 were XX, and 730 were XY (54:46 ratio). Aneuploidies were detected in 484 (21.8%) embryos. Aneuploidies related to X chromosome (XO or multiple X) were the most common (62.2%). In 12% of cycles only XY embryos were found, while 13.5% of the cycles had only XX embryos. A total of 593 (1.7 F 0.8) wanted embryos were transferred in 354 cycles. The outcome of 92 pregnancies will be discussed. Conclusion: PGD for gender selection for non-medical reasons can be applied within strict guidelines that should be developed for each cultural context. In 4 years of experience, only limited number of families asked for it. The inclusion of couples according to certain criteria maintained a positive social effect such as family and marital harmony, and reduced financial burden for couples. The technique is accurate and reliable. Longterm follow-up of born children has to be evaluated. D 2004 Elsevier B.V. All rights reserved. Keywords: Non-medical gender selection; PGD; ICSI
1. Introduction Population-based studies showed balanced societies in male to female sex ratio [1]. However, wars influenced the balance in favor of the female gender. Although societies on longitudinal dimension are balanced, certain families have children of one particular gender only and wish to have offspring of the opposite one a ‘‘balanced family’’ [2]. The couples request or choice to have children of certain gender is usually influenced by
* Tel.: +962-6-4603555; fax: +962-6-4614440. E-mail address: [email protected] (Z. Kilani). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.05.126
346
Z. Kilani / International Congress Series 1271 (2004) 345–348
certain social, cultural, religious and economic factors, e.g. some cultures want males as worriers, others as farmers, others to avoid certain social stigma, etc. Gender selection for non-medical reasons have been practiced by couples since ancient times. Myths dominated human thinking initially such as tying a string around the left testicle would make a boy, and around the right testicle would make a girl. Currently, there are different methods available for gender selection such as gender-selective insemination, gender-selective abortion, and gender-selective embryo transfer. There is as yet no convenient method for gender selection. Sex-selective insemination is still at large inaccurate, sex-selective abortion requires the hard decision to terminate an existing pregnancy, and sex-selective embryo transfer which involves IVF and PGD [3]. The availability of PGD for gender selection as a reliable and accurate method not only raised hopes, but also serious moral, legal, social, and religious concerns. 2. Materials and methods In the period between March 1998 till June 2003, 353 fertile couples who have at least three children of one gender only underwent 495 ICSI-PGD cycles for gender selection. In 490 cycles, couples had at least three daughters and wished to have a son, while in the other 5 cycles couples requested to have a daughter. Couples were counseled regarding the different options available including success rates, cost and the side effects of induction treatments. The cases were reviewed by the hospital ethical committee on individual basis and subsequently approved. The wives underwent standard superovulation using either the long or short protocols. Human chorionic gonadotropin was given for the final follicular maturation and oocyte pick-up was scheduled after 34 – 36 h. ICSI was performed and subsequently embryos were subjected to biopsy on day 3. Blastomeres were subjected to PGD using FISH technique for X and Y chromosomes. After each case approval, a discussion with the couple was made including screening for available chromosomal abnormalities (13, 16, 18 and 21). The desired embryos were replaced on day 4. The luteal phase was supported using either oral or vaginal progesterone. Pregnancy test in the serum was performed 12 days after ET. 3. Results As shown in Table 1, abnormalities related to X and or Y chromosomes were detected in 21.8% of the embryos. When screening for other chromosomes was included, single additional aneuploidy was found in 9.1% and complex aneuploidy was diagnosed in 23.1% of the embryos. Table 1 The result of chromosome analysis using FISH technique
Embryos analyzed (2216) 1 aneuploidy (13, 16, 18 21) Two or more aneuploidy (13, 16, 18, 21)
XX (38.1%)
XY (32.9%)
X,Y aneuploidy (21.8%)
No diagnosis (7.1%)
845 94 (11.1%) 32 (3.8%)
730 90 (12.3%) 34 (1.7%)
484 (21.8%) 44 (9.1%) 112 (23.1%)
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Z. Kilani / International Congress Series 1271 (2004) 345–348
347
Table 2 Pregnancy outcome of transferred cycles Transferred cycles
354 (278 patients)
Age (mean F S.D.) ET (mean F S.D.) Pregnancy Miscarriage Ectopic Delivered Lost contact
34.7 F 4.8 1.7 F 0.8 92 (26%) 33 2 53 4
A total of 53 deliveries: 39 singleton, 13 twins and 1 triplet were of the wanted gender. One male had Beckwith – Weidman syndrome. In four cases, follow-up was not possible after confirmation of pregnancy.
In 468 cycles where couples had three or more female daughters, mixed gender embryos were diagnosed in 349 (74.5%) cycles, while in 56 (12%) cycles only male embryos were found, and in 63 (13.5%) cycles only female embryos were diagnosed. Embryo transfer was cancelled in a total of 141 cycles: in 89 (63.1%) cycles for unwanted gender embryos, and in 53 (36.9%) cycles for the availability of aneuploid embryos only. Diagnosis was not achieved in 157 (7.1%) of the embryos. Failure to achieve diagnosis was due to the failure of signal appearance. Two hundred and seventy-eight patients underwent 354 transfer cycles: 221 patients had one transfer cycles, 40 patients had two transfer cycles, 15 patients had three transfer cycles and 2 patients had four transfer cycles (Table 2). 4. Discussion In the same period, the center dealt with around 17,000 ICSI cycles for infertility. Out of these cycles, 495 (2.9 %) cycles were conducted for gender selection for non-medical reasons. The couples were included according to strict guidelines adopted by the Farah hospital based upon special considerations: number of children of certain gender, maternal age, the loss of a child of certain gender with the desire to have another child of the same gender [4]. In our experience, all children born were of the selected gender. In a cultural context like ours which is situated in a predominantly Islamic environment, there is a high premium placed on couples to have at least one male offspring. Among the most pressing motivations for gender selection in such a culture are laws of inheritance which are extrapolated from the Islamic religion that require the presence of a male offspring to preserve the wealth within the family. Thus the presence of a male child is viewed as vital to the financial and social security of a family. The traditional option to most couples is to keep trying till they achieve their goal. This will usually result in larger family size, multiple marriages, and so adding to the financial burden of the family and society. In some areas, mid-trimester termination of pregnancy and even infanticide are practiced. Reviewing the religious perspectives, it is known according to the Jewish law that one son is required in order to fulfill criteria of procreation. Therefore the issue of pre-conceptional gender selection for non-medical indications is viewed as a reasonable consideration. On the other hand, according to the Christian view, gender pre-selection is forbidden even for
348
Z. Kilani / International Congress Series 1271 (2004) 345–348
medical indications. In Islam, pre-conceptional gender selection for non-medical reasons is legal when practiced on individual basis within strict guidelines [5]. Out of 68 children born, only 1 male baby was found to have Beckwith – Wiedemann syndrome. This syndrome may attributed to assisted reproductive technique since there are reports which claim higher incidence of this abnormality in IVF-ICSI babies [6]. So far more than 7000 PGD cycles have been conducted worldwide that resulted in delivery of more than 1000 babies apparently healthy and unaffected which supports the safety and reliability of such technique. However, the long-term mutagenic risks of the gender selection procedure to children born must be followed up and evaluated after few years. Since gender selection for non-medical reasons causes no harm to others, a legal ban seems unjustified. The Ethics Committee of the ASRM, in its May 2001 Committee Report [3], reached the principal conclusion that gender selection for non-medical reason was under certain circumstances, an ethically appropriate medical procedure. The availability of sex selection using PGD particularly within certain cultural context does have a positive social effect: it maintains family harmony, reduces long-term financial burden for the couple and supports the ethical principle of autonomy, beneficence and nonmaleficence. However, this does not preclude regulating its practice, such as limiting the practice to licensed centers with strict guidelines and regulations that can guarantee high scientific standards and quality professional care. References [1] United Nations Population Division (UNPD), Sex and Age 1950 – 2025 (The 1992 Revision), on diskette (UNPD, New York, 1992), Data refer to 1990. [2] H. Straghtam, et al., Choice of baby’s sex, Lancet 341 (1993) 564 – 565. [3] Ethics Committee of the American Society of Reproductive Medicine, Preimplantation genetic diagnosis and sex selection, Fertil. Steril. 72 (1999) 595 – 598. [4] Z. Kilani, L. Haj Hassan, Sex selection and preimplantation genetic diagnosis at The Farah Hospital. Reproductive Biomedicine Online 4 (1) 68 – 70. [5] J.G. Schenker, Gender selection: cultural and religious perspectives, J. Assist Reprod. Genet. 19 (9) (2002 Sep.) 400 – 410. [6] F. Olivennes, et-al., Prenatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF: a preliminary report, Hum. Reprod. 16 1588 – 1591.
www.ics-elsevier.com
Controversies in gender selection Zaid Kilani * The Farah Hospital, May Ziadeh Street, P.O. Box 5323, Jabal Amman, 4th Circle, Amman 11183, Jordan
Abstract. Introduction: The issue of gender determination is an old one. It was practiced in a way or another all through ages. The traditional option available for couples is to keep trying in the hope of achieving their goal. Different options include sperm separation and selective termination of pregnancy. Preimplantation genetic diagnosis (PGD) offered an accurate method which guarantees the transfer of the wanted gender. The application of PGD for that purpose had been the subject of heated debate and complex ethical arguments. We will extend and express some views based upon practical experience regarding the application of PGD for gender selection. Methods: After approval of the hospital ethical committee, 495 IVF-ICSI cycles were initiated over 4 years of experience. In 490 cycles couples had at least three daughters and wished to have a son. Out of 2445 embryos obtained, 2216 (90.6%) embryos were biopsied on day 3 and analyzed using fluorescent in situ hybridization (FISH) for X,Y. Chromosomes 13,16,18,21 were included upon request. Results: Out of the 2216 embryos analyzed, 845 were XX, and 730 were XY (54:46 ratio). Aneuploidies were detected in 484 (21.8%) embryos. Aneuploidies related to X chromosome (XO or multiple X) were the most common (62.2%). In 12% of cycles only XY embryos were found, while 13.5% of the cycles had only XX embryos. A total of 593 (1.7 F 0.8) wanted embryos were transferred in 354 cycles. The outcome of 92 pregnancies will be discussed. Conclusion: PGD for gender selection for non-medical reasons can be applied within strict guidelines that should be developed for each cultural context. In 4 years of experience, only limited number of families asked for it. The inclusion of couples according to certain criteria maintained a positive social effect such as family and marital harmony, and reduced financial burden for couples. The technique is accurate and reliable. Longterm follow-up of born children has to be evaluated. D 2004 Elsevier B.V. All rights reserved. Keywords: Non-medical gender selection; PGD; ICSI
1. Introduction Population-based studies showed balanced societies in male to female sex ratio [1]. However, wars influenced the balance in favor of the female gender. Although societies on longitudinal dimension are balanced, certain families have children of one particular gender only and wish to have offspring of the opposite one a ‘‘balanced family’’ [2]. The couples request or choice to have children of certain gender is usually influenced by
* Tel.: +962-6-4603555; fax: +962-6-4614440. E-mail address: [email protected] (Z. Kilani). 0531-5131/ D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ics.2004.05.126
346
Z. Kilani / International Congress Series 1271 (2004) 345–348
certain social, cultural, religious and economic factors, e.g. some cultures want males as worriers, others as farmers, others to avoid certain social stigma, etc. Gender selection for non-medical reasons have been practiced by couples since ancient times. Myths dominated human thinking initially such as tying a string around the left testicle would make a boy, and around the right testicle would make a girl. Currently, there are different methods available for gender selection such as gender-selective insemination, gender-selective abortion, and gender-selective embryo transfer. There is as yet no convenient method for gender selection. Sex-selective insemination is still at large inaccurate, sex-selective abortion requires the hard decision to terminate an existing pregnancy, and sex-selective embryo transfer which involves IVF and PGD [3]. The availability of PGD for gender selection as a reliable and accurate method not only raised hopes, but also serious moral, legal, social, and religious concerns. 2. Materials and methods In the period between March 1998 till June 2003, 353 fertile couples who have at least three children of one gender only underwent 495 ICSI-PGD cycles for gender selection. In 490 cycles, couples had at least three daughters and wished to have a son, while in the other 5 cycles couples requested to have a daughter. Couples were counseled regarding the different options available including success rates, cost and the side effects of induction treatments. The cases were reviewed by the hospital ethical committee on individual basis and subsequently approved. The wives underwent standard superovulation using either the long or short protocols. Human chorionic gonadotropin was given for the final follicular maturation and oocyte pick-up was scheduled after 34 – 36 h. ICSI was performed and subsequently embryos were subjected to biopsy on day 3. Blastomeres were subjected to PGD using FISH technique for X and Y chromosomes. After each case approval, a discussion with the couple was made including screening for available chromosomal abnormalities (13, 16, 18 and 21). The desired embryos were replaced on day 4. The luteal phase was supported using either oral or vaginal progesterone. Pregnancy test in the serum was performed 12 days after ET. 3. Results As shown in Table 1, abnormalities related to X and or Y chromosomes were detected in 21.8% of the embryos. When screening for other chromosomes was included, single additional aneuploidy was found in 9.1% and complex aneuploidy was diagnosed in 23.1% of the embryos. Table 1 The result of chromosome analysis using FISH technique
Embryos analyzed (2216) 1 aneuploidy (13, 16, 18 21) Two or more aneuploidy (13, 16, 18, 21)
XX (38.1%)
XY (32.9%)
X,Y aneuploidy (21.8%)
No diagnosis (7.1%)
845 94 (11.1%) 32 (3.8%)
730 90 (12.3%) 34 (1.7%)
484 (21.8%) 44 (9.1%) 112 (23.1%)
157
Z. Kilani / International Congress Series 1271 (2004) 345–348
347
Table 2 Pregnancy outcome of transferred cycles Transferred cycles
354 (278 patients)
Age (mean F S.D.) ET (mean F S.D.) Pregnancy Miscarriage Ectopic Delivered Lost contact
34.7 F 4.8 1.7 F 0.8 92 (26%) 33 2 53 4
A total of 53 deliveries: 39 singleton, 13 twins and 1 triplet were of the wanted gender. One male had Beckwith – Weidman syndrome. In four cases, follow-up was not possible after confirmation of pregnancy.
In 468 cycles where couples had three or more female daughters, mixed gender embryos were diagnosed in 349 (74.5%) cycles, while in 56 (12%) cycles only male embryos were found, and in 63 (13.5%) cycles only female embryos were diagnosed. Embryo transfer was cancelled in a total of 141 cycles: in 89 (63.1%) cycles for unwanted gender embryos, and in 53 (36.9%) cycles for the availability of aneuploid embryos only. Diagnosis was not achieved in 157 (7.1%) of the embryos. Failure to achieve diagnosis was due to the failure of signal appearance. Two hundred and seventy-eight patients underwent 354 transfer cycles: 221 patients had one transfer cycles, 40 patients had two transfer cycles, 15 patients had three transfer cycles and 2 patients had four transfer cycles (Table 2). 4. Discussion In the same period, the center dealt with around 17,000 ICSI cycles for infertility. Out of these cycles, 495 (2.9 %) cycles were conducted for gender selection for non-medical reasons. The couples were included according to strict guidelines adopted by the Farah hospital based upon special considerations: number of children of certain gender, maternal age, the loss of a child of certain gender with the desire to have another child of the same gender [4]. In our experience, all children born were of the selected gender. In a cultural context like ours which is situated in a predominantly Islamic environment, there is a high premium placed on couples to have at least one male offspring. Among the most pressing motivations for gender selection in such a culture are laws of inheritance which are extrapolated from the Islamic religion that require the presence of a male offspring to preserve the wealth within the family. Thus the presence of a male child is viewed as vital to the financial and social security of a family. The traditional option to most couples is to keep trying till they achieve their goal. This will usually result in larger family size, multiple marriages, and so adding to the financial burden of the family and society. In some areas, mid-trimester termination of pregnancy and even infanticide are practiced. Reviewing the religious perspectives, it is known according to the Jewish law that one son is required in order to fulfill criteria of procreation. Therefore the issue of pre-conceptional gender selection for non-medical indications is viewed as a reasonable consideration. On the other hand, according to the Christian view, gender pre-selection is forbidden even for
348
Z. Kilani / International Congress Series 1271 (2004) 345–348
medical indications. In Islam, pre-conceptional gender selection for non-medical reasons is legal when practiced on individual basis within strict guidelines [5]. Out of 68 children born, only 1 male baby was found to have Beckwith – Wiedemann syndrome. This syndrome may attributed to assisted reproductive technique since there are reports which claim higher incidence of this abnormality in IVF-ICSI babies [6]. So far more than 7000 PGD cycles have been conducted worldwide that resulted in delivery of more than 1000 babies apparently healthy and unaffected which supports the safety and reliability of such technique. However, the long-term mutagenic risks of the gender selection procedure to children born must be followed up and evaluated after few years. Since gender selection for non-medical reasons causes no harm to others, a legal ban seems unjustified. The Ethics Committee of the ASRM, in its May 2001 Committee Report [3], reached the principal conclusion that gender selection for non-medical reason was under certain circumstances, an ethically appropriate medical procedure. The availability of sex selection using PGD particularly within certain cultural context does have a positive social effect: it maintains family harmony, reduces long-term financial burden for the couple and supports the ethical principle of autonomy, beneficence and nonmaleficence. However, this does not preclude regulating its practice, such as limiting the practice to licensed centers with strict guidelines and regulations that can guarantee high scientific standards and quality professional care. References [1] United Nations Population Division (UNPD), Sex and Age 1950 – 2025 (The 1992 Revision), on diskette (UNPD, New York, 1992), Data refer to 1990. [2] H. Straghtam, et al., Choice of baby’s sex, Lancet 341 (1993) 564 – 565. [3] Ethics Committee of the American Society of Reproductive Medicine, Preimplantation genetic diagnosis and sex selection, Fertil. Steril. 72 (1999) 595 – 598. [4] Z. Kilani, L. Haj Hassan, Sex selection and preimplantation genetic diagnosis at The Farah Hospital. Reproductive Biomedicine Online 4 (1) 68 – 70. [5] J.G. Schenker, Gender selection: cultural and religious perspectives, J. Assist Reprod. Genet. 19 (9) (2002 Sep.) 400 – 410. [6] F. Olivennes, et-al., Prenatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF: a preliminary report, Hum. Reprod. 16 1588 – 1591.