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Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002 ( C 2002)




                                                                                          Regional–Geographic Views

The 50 Million Missing Women
Gautam N. Allahbadia1




                                  Submitted March 14, 2002; accepted April 1, 2002

                                  The epidemic of gender selection is ravaging countries like India & China. Approximately fifty
                                  million women are “missing” in the Indian population. Generally three principle causes are
                                  given: female infanticide, better food and health care for boys and maternal death at childbirth.
                                  Prenatal sex determination and the abortion of female fetuses threatens to skew the sex ratio
                                  to new highs. Estimates of the number of female fetuses being destroyed every year in India
                                  vary from two million to five million. This review from India attempts to summarize all the
                                  currently available methods of sex selection and also highlights the current medical practice
                                  regards the subject in south-east Asia.
                                  KEY WORDS: Sex selection; fetal sex determination.




         Application of technology should be in                          of a desired sex. In a male-oriented society such as
         consonance with the laws of nature.                             India, the commonest methods employed by the vast
                                                                         majority of the populace, usually after two female
                        —Dr A.P.J. Abdul Kalam
                                                                         children is ultrasound directed fetal sex determination
                                       Director
                                                                         at 13/14 weeks gestational age and in more affluent
                Defence Research & Development
                                                                         urban areas the chorionic villus sampling technique
                             Organization, India
                                                                         at 8/9 weeks. Sex selection has become a national
                                                                         crisis in India and China, where cheap mobile ul-
INTRODUCTION                                                             trasound clinics travel the countryside testing preg-
                                                                         nant women. Women who discover that their fetus
We are not talking about long-range nuclear-tipped                       is female often opt for legal abortions referred to
missiles here, but this quote applies to the epidemic                    as MTPs (Medical Termination of Pregnancy). Es-
of gender selection that is ravaging countries such as                   timates of the number of female fetuses being de-
India and China. Approximately 50 million women                          stroyed every year in India vary from two million to
are “missing” in the Indian population. Generally                        five million. This practice has reportedly skewed sex
three principal causes are given: female infanticide,                    ratios from the natural 106 boys to 100 girls to as high
better food and health care for boys, and mater-                         as 130 boys to 100 girls. Such results led both China
nal death at childbirth. The situation is similar in                     and India to ban ultrasound testing for the purpose
China and other Asian and Middle Eastern countries.                      of sex selection. Recognizing and seeking to control
Prenatal sex determination and the abortion of fe-                       this perilous trend, the government of India outlawed
male fetuses threatens to skew the sex ratio to new                      prenatal sex determination on January 1, 1996. The
highs—with unknown consequences. Various meth-                           new law makes it illegal to advertise or perform the
ods now exist for attempting to choose to have a baby                    tests (with a few exceptions) and punishes the doc-
                                                                         tor as well as relatives who encourage the test and
1
                                                                         the woman herself with fines from 10 to 50 thou-
    Rotunda – The Center For Human Reproduction, 672 Kalpak
    Gulistan, Perry Cross Road, Near Otters Club, Bandra, Mumbai         sand rupees and jail terms from 3 to 5 years. But all
    400 050 India; e-mail: gautam@rotundaivf.com.                        that this act did was to bring about an entirely new


                                                                   411                    1058-0468/02/0900-0411/0   C   2002 Plenum Publishing Corporation
412                                                                                                                 Allahbadia


underground market for sex determinations. Doctors              obtaining a desired pregnancy gender outcome that
now charge a premium for the services. In a bureau-             ranges from excellent to virtually guaranteed.
cratic administrative setup, this gave corrupt govern-             Some natural gender selection methods are based
ment officials a lucrative business opportunity to ex-           on the observation that a conception attempt, relative
tort bribes from flourishing sex selection clinics across        to ovulation, is more likely to result in the concep-
the country.                                                    tion of a specific sex. Attempts to time conception for
                                                                a specific sex relative to ovulation have been made
HISTORICAL DEVELOPMENTS                                         by measuring hormonal levels, basal body tempera-
                                                                ture, and cervical mucus observations. Other natural
   Attempts to select children’s sex have a long history,       methods include radical diets, frequency and positions
from the herbal nostrums recommended by tradi-                  of intercourse, vaginal douching, etc. These methods
tional healers to more recent therapists’ advice about          are commonly used throughout the world, but the ef-
which forms of intercourse are allegedly likely to pro-         fectiveness of these natural gender selection methods
duce girls or boys. The selection of gender has been            have not been well documented.
a quest of couples for as far back as recorded history
allows. Early drawings from prehistoric times suggest           MORE RECENT DEVELOPMENTS
that sex selection efforts were being investigated by
our earliest ancestors. Later history shows intense in-            Timing intercourse for gender selection is based
terest in sex selection by early Asian, Egyptian, and           on the life and mobility of sperm; it has been sug-
Greek cultures. Anaxagoras, a fifth century B.C. Greek           gested that the androsperm (Y-bearing sperm) are
philosopher, believed that semen from the right tes-            stronger and faster but do not survive for very long.
ticle produced sons, while semen from the left testi-           Gynosperm, (X-bearing sperm), on the other hand,
cle resulted in the birth of a daughter. Believing the          are slower but have greater staying power, conse-
same theory, men in the Balkans would squeeze the               quently a longer life span (1). Intercourse position is
right side of their scrotums in the hope of increasing          also based on the mobility of sperm, with shallow pen-
the odds of having a son. A misconception that per-             etration (missionary position) favoring the concep-
sisted till as late as the sixteenth century was that male      tion of a baby girl, with deep penetration (rear entry)
babies developed in the right side of the uterus. The           favoring the conception of a baby boy (1). The Whelan
Perfumed Garden, written by Shaikh Nefwazi, recom-              Method is in complete disagreement with the Shettles
mended turning the woman on her right side after the            method and suggests the opposite (2). Whelan says
man had ejaculated. The Charaka Samhita, a man-                 to have intercourse 4–6 days so as to conceive a
ual written around 800 B.C. in India, advised prospec-          boy before your basal body temperature goes up.
tive parents who expressed a preference for sons that           To conceive a girl, intercourse should occur 2–3 days
they should “abstain from intercourse for a week, gaz-          before ovulation.
ing every morning and evening upon a majestic white                In 1984, the World Health Organization published
bull or stallion, being entertained by pleasant tales,          a study that failed to confirm gender predominance
and feeding their eyes on men and women of gentle               when timing conception relative to ovulation (3). Un-
looks.” Mistaking vaginal secretions for semen, an-             terburger had made observations with respect to al-
cient Greek, Hebrew, and Indian literature stated that          kalinity and acidity and gender predetermination (4).
both men and women produced semen. Sons were                    Women recommended to use an alkaline douche (for
born when the male semen was predominant. Mas-                  overcoming fertility problems) conceived a higher
turbation after a period of sexual abstinence usually           than usual number of boys (4).
results in the ejaculation of a greater amount of se-              Langendoen and Proctor first published The Pre-
men. Based on this observation, sexual abstinence was           Conception Gender Diet in 1982, on the basis of re-
recommended for men who wanted sons. An ancient                 sults reported by Stolkowski and Lorrain in 1980 (5).
Chinese birth chart predicts sex of the child based on          The theory is that by altering your diet to include and
the age of the mother at conception and the month of            exclude certain foods, the conditions in the reproduc-
conception. This is followed by documented scientific            tive tract will be directly affected, increasing the odds
efforts beginning in the 1600s to sway the chances of           of conceiving a particular sex. This theory is also con-
achieving a pregnancy by a variety of methods. Re-              sistent with the oriental philosophy that everything
search and work carried out in the 1980s and 1990s              has a yin or yang quality and the foods supplied in
have finally provided methods offering the chance of             the boy diet (boys and alkaline) are all yang and the

                                                     Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
The 50 Million Missing Women                                                                                                 413


foods supplied in the girl diet (girls and acid) are all                ferent concentrations, and the Y and X sperm are be-
yin. Claims of 80% accuracy, based on one clinical                      lieved to be partially separated at low speed inside a
trial of only 260 women, the results were published in                  centrifuge by their differential sedimentation veloci-
the International Journal of Gynaecology and Obstet-                    ties. The rationale to this treatment is that the X sperm
rics in 1980 (5). The girl diet is high in calcium but low              is believed to be bigger and heavier than the Y sperm
in salt and potassium, containing acid-forming foods.                   and it will sediment down the Percoll gradient quicker
The boy diet is high in salt and potassium but low in                   under centrifugation. If sperm collected at the bottom
calcium and magnesium and contains alkali-forming                       of the Percoll gradient are used for artificial insemi-
foods.                                                                  nation, the chances for conceiving a girl should be
   The majority of the artificial sex selection meth-                    greater.
ods work by separating X- and Y- bearing sperm and                         With the recent advent of Microsort (flow cytomet-
require artificial insemination. The Ericsson Method                     ric separation of X and Y sperm) and preimplanta-
was developed about 25 years ago and has been in clin-                  tion genetic diagnosis (PGD), couples no longer have
ical use for the last 20 years. Currently, there are over               an excuse to employ abortions to select sex. The Mi-
40 Sperm Centers using this procedure in the world,                     crosort method is an expensive approach to gender se-
and over 2000 healthy babies have been born using                       lection involving the separation of the X sperm from
the albumin treatment, the great majority of them in                    the Y sperm. This method uses a technique known
the United States.                                                      as flow cytometry where seminal fluid is filtered and
   The treatment for conception of a boy involves run-                  then forced through a long, thin tube under pres-
ning the husband’s sperm sample through columns                         sure. At the other end, the tube divides, and there
containing human serum albumin solutions of differ-                     is a fluorescence-based switch, designed to direct the
ent concentrations by which Y-bearing sperm can be                      larger X sperm into one direction, and the smaller
separated through a filtering process (6). In January                    Y sperm into a different direction. The desired X-rich
1998, Hong Kong researchers who used the Ericsson                       or Y-rich sperm samples can then be used for artificial
method (7) published a paper. They did DNA stud-                        insemination (11).
ies on the supposedly X-rich and Y-rich samples pro-
duced by the separation and found that each sample                      CULTURAL ISSUES
still contained the original 50% ratio of X-bearing to
Y-bearing sperm. Many have claimed success at this                         The problem with trying to prevent couples from
type of sperm separation, but few have been able to                     aborting female fetuses is that cultural traditions die
back up their claims with hard data.                                    hard, and a particularly powerful one is that boys are
   There have been several reports in the scientific lit-                infinitely more desirable than girls. The reason is sim-
erature recently which suggest that sperm subjected                     ple: when parents marry off a daughter, society ex-
to a swimup procedure and used for artificial insemi-                    pects them to give a huge dowry to the boy’s family.
nation can increase the chances of conceiving a male                    This represents an enormous burden that often wipes
by between 80 and 90%. In one study carried out in                      out a family’s entire savings. Recent advertisements
1993, 23 of 26 births were male claiming a success                      in the national press and on the internet extolling the
rate of about 88.5% for male sex selection (8). Two                     “highly effective” gender selection kit marketed by a
recent studies suggest that the Percoll density gra-                    U.S. company has created a hornet’s nest. The govern-
dient method is effective in both separating the X                      ment is naturally perturbed about the ramifications
and Y sperm and also skewing the birth sex ratio in                     of such advertisements and its potential to skew the
humans (9,10).                                                          already-tilted female–male birth ratio in the country.
   A 1996 study suggested that bottom (X) fraction                      Recent editions of India Abroad, a weekly newspa-
sperm, derived from the eight-layer discontinuous                       per for Indian expatriates in the United States and
Percoll gradient, have higher motility, progression,                    Canada, are carrying sex preselection ads by compa-
and hyperactivation when compared with top (Y)                          nies to promote their products to one of the country’s
fraction sperm. The bottom (X) fraction sperm have                      fastest growing ethnic groups. And the target market
greater longevity in motility and have shorter tails,                   is immigrants from India, where sex-determination
supporting earlier hypotheses of sex differences in                     tests were outlawed 8 years ago in a still unsuccessful
sperm parameters (9). In the Percoll procedure, the                     effort to thwart the widespread practice of aborting fe-
sperm sample is layered on top of a Percoll density                     male fetuses. Such ads would be illegal in India, which
gradient consisting of many layers of Percoll at dif-                   has struggled for years to discourage women from

Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
414                                                                                                                  Allahbadia


exploiting medical technology to assure themselves               ics, buoyed by record profits, are aggressively selling
of giving birth to boys. Now, Indians in the United              their wares. One clever economic pitch blares from
States and Canada find themselves being courted by                tens of thousands of billboards through the country—
American companies that promise to help do just that.            Pay five hundred rupees [US$14.00] now rather than
   In India and China, female infanticide is both so-            five lakhs [Rs 500,000 or $14,000] later. Poor families,
cially sanctioned and undeserving of mourning. Yet,              fearing expensive dowries that can cripple a family,
one should consider it repugnant to kill the fetus by            willingly undergo the tests. Coming on top of more
way of abortion, especially when only done to abort              than a century of female infanticide in regions where
a girl fetus. This would appear even more the case               sons are preferred, medical technologies of amnio-
in our country where women deities are worshipped                centesis, ultrasound, and chorionic biopsy have com-
in various forms. In both Karnataka and Bengal the               pounded the problem of “missing females” over the
deities of the state is a goddess.                               past two decades. Despite the 1994 Prenatal Diagnos-
   Few of India’s states show the political will to en-          tic Techniques (Regulation and Prevention of Misuse)
force the century-old law prohibiting female infan-              Act in India and China’s Human Reproductive Tech-
ticide. A ritual which originated amongst certain of             nology Ordinance of 2000, sex determination for pur-
Rajasthan’s tribal communities, the murder of the girl           poses of aborting female fetuses is presently a highly
infant, is morally cleansed by the reasoning that killing        profitable medical industry. In India, the act is an “on-
takes place before the ritual bath, 7–10 days after              paper-only” law which has proven to be a toothless
birth, which grants an infant “human status.” This is            tiger in the face of blatant abuse by elements of the
further upheld by superstitions maintaining that the             medical fraternity. Some go so far as to suggest that
act enhances the chance of the next born being the               they are helping curb the population explosion. Oth-
preferred son.                                                   ers defend their lucrative business, saying it offers
   The killing of the infants, when born with deformi-           women a less barbaric means than female infanticide
ties of face and limbs, soon after the birth, is a frequent      of doing away with their daughters. Needless to say,
occurrence in India. The culprits are the dais (tradi-           not a single legal case has been registered in India
tional birth attendants) and old ladies who attend to            or China against those peddling their technological
child birth in rural communities. They, in their own             misogyny.
way, protect the family from the financial expenses                  Not surprisingly, proselective abortion activists feel
and social stigmas associated with bringing up such              that selective abortion has several merits important
a child in a country where a lack of social education            for the good of the general Indian public. For exam-
prevents these unfortunate infants from living a full            ple, advocates argue that selective abortion is the an-
life and rehabilitating them. The problem has taken              swer to population control. Perhaps they feel that in
monstrous proportions in just the past two decades.              a country where families are willing to have child af-
   Prenatal techniques for sex determination were in-            ter child until they have their desired number of sons
troduced into India only in the early 1970s. Although            and daughters, sex selective abortions would allow
touted officially as an aid in reducing genetic defects,          women to choose the makeup of their family while
much of the Indian public has turned to these tests to           keeping the family size small. Another argument in
find out if “It’s a boy” or not. The effects of these de-         terms of population control is that families should be
velopments on sex ratio can be observed in every class           balanced; selective abortions will allow families to bal-
of the society. An awareness program going right to              ance their desire for a daughter with one for a son. It’s
the grass-roots level and effective deterrent punish-            a gut-wrenching fact that in a patriarchal country like
ment to doctors who flout the law may be a solution.              India, where sons are prized and daughters devalued
   The proliferation, and increasingly reported abuse,           in society for a variety of reasons, it is likely that cou-
of prenatal testing has forced an impassioned debate             ples will choose to abort only females.
throughout India. Those fighting against the tests cite
studies which suggest that a further skewing of the sex
ratio may only make worse the status of women, with              RECENT CHANGES
an obvious negative impact on the whole nation. On
the other hand, there is a great deal of public support             In India, requests for medically assisted sex selec-
in India from prosex selective abortion advocates who            tion are very common; for example, one fertility clinic
feel that these tools are helping families to cope with          in Mumbai used to receive about 250–300 requests for
intransigent problems, especially dowry. Health clin-            Y-enrichment with intrauterine inseminations each

                                                      Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
The 50 Million Missing Women                                                                                                    415


year till the time the Prenatal Diagnosis Act was ex-                   in subsequent treatment cycles. This has advantages in
tended in 2002 to include sex selection using sperm                     both reducing the cost of further treatment and min-
separation techniques as well. Imprisonment for up to                   imizing greatly the number of unwanted embryos.
3 years is the deterrent used by the Union government                      Sex selection is controversial because it is the first
against medical practitioners who continue to do sex                    example of genetic selection for a nondisease trait.
determination tests. As I write this paper, the scenario                Being a boy or a girl is not a disease. So should par-
truly appears to change, and in 2002 the government                     ents be permitted to select traits other than the sex of
seems serious and has really clamped down on clinics                    their children? Few aspects of human development
offering sex selection or sex determination. Every ul-                  are more significant than one’s sex; it’s a central fact
trasound machine manufacturer has to furnish a list                     of one’s identity as a human being. If it is ethically
of the doctors to whom their units have been sold,                      permissible for parents to make that choice, the case
and these doctors now have to compulsorily register                     for letting them make less significant genetic choices
with the government and put up boards outside their                     for their offspring is already made. In an ethical state-
clinics proclaiming that This clinic does not perform                   ment issued last year, the American Society for Re-
any sex determination.                                                  productive Medicine concluded that if Preconcep-
                                                                        tional Sex Selection is found to be safe and effective,
                                                                        “physicians should be free to offer pre-conception
PGD FOR SEX SELECTION                                                   gender selection in clinical settings to couples who
                                                                        are seeking gender variety in their offspring” (13).
   There is a very affluent trader community in                          Some others see the use of preimplantation sex se-
India whose religious beliefs do not allow medical ter-                 lection as a slippery slope to eugenics, since the
mination of pregnancy. It is this rich, male-oriented                   same techniques can be used to test for other genetic
community that has spawned a whole new breed of                         traits.
fertility clinics attempting to offer PGD-IVF for selec-                   They might want to ponder the story of 6-year-old
tive transfer of male embryos. Each attempt of PGD-                     Molly Nash, who suffered from the fatal genetic dis-
IVF for transfer of male embryos can cost as much                       ease, Fanconi anemia. The only cure for Molly’s dis-
as US$5000 even in a “developing” country such as                       ease is a bone marrow transplant from a compatible
India, where more than 50% of the populace lives be-                    donor. Her parents used preimplantation genetic test-
low the poverty line. Sex selection may, therefore, be-                 ing to help them bear a sibling who would be a per-
come more acceptable to some couples, and requests                      fect genetic match for her. Using IVF, Molly’s parents
for clinics to provide it may become more common.                       produced 30 embryos that were tested for the dis-
   IVF techniques for gender selection began with                       ease gene and for transplant compatibility. Only five
a single cell being removed from an eight-cell em-                      had the right genetic makeup. The fourth attempted
bryo under the microscope. The cell was then ana-                       pregnancy resulted in the birth of Adam Nash in
lyzed for genetic disorders and/or gender by FISH                       August 2000. His umbilical cord blood stem cells were
(Fluorescence in situ hybridization). The FISH tech-                    used to replace Molly’s defective marrow, and now
nique utilizes fluorescent probes which are specified                     both children are healthy. Few people would regard
for chromosomes. This technique is used for sex de-                     what Molly’s parents did as immoral. After all, genetic
termination and for structural chromosomal abnor-                       testing in this case resulted in two valued and healthy
malities and allows to select only the chromosoma-                      children.
lly normal embryos with the desired sex for embryo                         Therefore, I strongly believe that it is sometimes
transfer (8). At the 8- or 16-cell stage, embryos can                   ethical to let parents choose their children’s sex.
be sexed very reliably by removing one or two cells
and sexing these with FISH or PCR methods (12).                         REFERENCES
Once the genders of all the embryos have been de-
termined, the embryos (normally between two and                          1. Shettles LB: Letter: Sex selection. Am J Obstet Gynecol
four are transferred depending on the woman’s age)                          1976;124(4):441–442
of the desired sex are then replaced in the uterus. By                   2. Daniell JF: Sex-selection procedures. J Reprod Med
                                                                            1983;28(4):235–237
combining the IVF method with sperm sorting, using
                                                                         3. World Health Organization: A prospective multi-centre
Microsort technology, the number of male or female                          study of the ovulation method of Natural Family Planning
embryos could be greatly enhanced, and those em-                            for the outcome of pregnancy. Fertil Steril 1984;41:593–
bryos that are not replaced can be frozen and be used                       598


Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
416                                                                                                                           Allahbadia


4. Gledhill BL: Gender preselection: Historical, technical, and                on discontinuous Percoll gradient for sex preselection: Com-
   ethical perspectives. Semin Reprod Endocrinol 1988;6(4):385–                puterized analyses. Arch Androl 1996;37(1):1–5
   395                                                                   10.   Wang JX, Flaherty SP, Matthews CD: Sperm separation for sex
5. Stolkowski J, Lorrain J: Preconceptional selection of fetal sex.            selection. Hum Reprod 1998;13(9):2659–2661
   Int J Gynaecol Obstet 1980;18(6):440–443                              11.   Fugger EF, Black SH, Keyvanfar K, Schulman JD: Births
6. Ericsson SA, Ericsson RJ: Sex ratio of male sex preselected                 of normal daughters after Microsort sperm separation and
   children born to couples with exclusively female offspring.                 intrauterine insemination, in-vitro fertilization, or intra-
   Arch Androl 1992;28(2):121–123                                              cytoplasmic sperm injection. Hum Reprod 1998;13:2367–
7. Rose GA, Wong A: Experiences in Hong Kong with the theory                   2370
   and practice of the albumin column method of sperm separa-            12.   Sills ES, Goldschlag D, Levy DP, Davis OK, Rosenwaks Z:
   tion for sex selection. Hum Reprod 1998;13(1):146–149                       Preimplantation genetic diagnosis: Considerations for use in
8. Check JH, Katsoff D: A prospective study to evaluate the ef-                elective human embryo sex selection. J Assist Reprod Genet
   ficacy of modified swim-up preparation for male sex selection.                1999;16(10):509–511
   Hum Reprod 1993;8(2):211–214                                          13.   Ethics Committee of the American Society for Reproduc-
9. Watkins AM, Chan PJ, Patton WC, Jacobson JD, King A:                        tive Medicine. Preconception gender selection for non medical
   Sperm kinetics and morphology before and after fractionation                reasons. Fertil Steril 2001;75(5):861–864




                                                              Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002

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50 million missing women

  • 1. Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002 ( C 2002) Regional–Geographic Views The 50 Million Missing Women Gautam N. Allahbadia1 Submitted March 14, 2002; accepted April 1, 2002 The epidemic of gender selection is ravaging countries like India & China. Approximately fifty million women are “missing” in the Indian population. Generally three principle causes are given: female infanticide, better food and health care for boys and maternal death at childbirth. Prenatal sex determination and the abortion of female fetuses threatens to skew the sex ratio to new highs. Estimates of the number of female fetuses being destroyed every year in India vary from two million to five million. This review from India attempts to summarize all the currently available methods of sex selection and also highlights the current medical practice regards the subject in south-east Asia. KEY WORDS: Sex selection; fetal sex determination. Application of technology should be in of a desired sex. In a male-oriented society such as consonance with the laws of nature. India, the commonest methods employed by the vast majority of the populace, usually after two female —Dr A.P.J. Abdul Kalam children is ultrasound directed fetal sex determination Director at 13/14 weeks gestational age and in more affluent Defence Research & Development urban areas the chorionic villus sampling technique Organization, India at 8/9 weeks. Sex selection has become a national crisis in India and China, where cheap mobile ul- INTRODUCTION trasound clinics travel the countryside testing preg- nant women. Women who discover that their fetus We are not talking about long-range nuclear-tipped is female often opt for legal abortions referred to missiles here, but this quote applies to the epidemic as MTPs (Medical Termination of Pregnancy). Es- of gender selection that is ravaging countries such as timates of the number of female fetuses being de- India and China. Approximately 50 million women stroyed every year in India vary from two million to are “missing” in the Indian population. Generally five million. This practice has reportedly skewed sex three principal causes are given: female infanticide, ratios from the natural 106 boys to 100 girls to as high better food and health care for boys, and mater- as 130 boys to 100 girls. Such results led both China nal death at childbirth. The situation is similar in and India to ban ultrasound testing for the purpose China and other Asian and Middle Eastern countries. of sex selection. Recognizing and seeking to control Prenatal sex determination and the abortion of fe- this perilous trend, the government of India outlawed male fetuses threatens to skew the sex ratio to new prenatal sex determination on January 1, 1996. The highs—with unknown consequences. Various meth- new law makes it illegal to advertise or perform the ods now exist for attempting to choose to have a baby tests (with a few exceptions) and punishes the doc- tor as well as relatives who encourage the test and 1 the woman herself with fines from 10 to 50 thou- Rotunda – The Center For Human Reproduction, 672 Kalpak Gulistan, Perry Cross Road, Near Otters Club, Bandra, Mumbai sand rupees and jail terms from 3 to 5 years. But all 400 050 India; e-mail: gautam@rotundaivf.com. that this act did was to bring about an entirely new 411 1058-0468/02/0900-0411/0 C 2002 Plenum Publishing Corporation
  • 2. 412 Allahbadia underground market for sex determinations. Doctors obtaining a desired pregnancy gender outcome that now charge a premium for the services. In a bureau- ranges from excellent to virtually guaranteed. cratic administrative setup, this gave corrupt govern- Some natural gender selection methods are based ment officials a lucrative business opportunity to ex- on the observation that a conception attempt, relative tort bribes from flourishing sex selection clinics across to ovulation, is more likely to result in the concep- the country. tion of a specific sex. Attempts to time conception for a specific sex relative to ovulation have been made HISTORICAL DEVELOPMENTS by measuring hormonal levels, basal body tempera- ture, and cervical mucus observations. Other natural Attempts to select children’s sex have a long history, methods include radical diets, frequency and positions from the herbal nostrums recommended by tradi- of intercourse, vaginal douching, etc. These methods tional healers to more recent therapists’ advice about are commonly used throughout the world, but the ef- which forms of intercourse are allegedly likely to pro- fectiveness of these natural gender selection methods duce girls or boys. The selection of gender has been have not been well documented. a quest of couples for as far back as recorded history allows. Early drawings from prehistoric times suggest MORE RECENT DEVELOPMENTS that sex selection efforts were being investigated by our earliest ancestors. Later history shows intense in- Timing intercourse for gender selection is based terest in sex selection by early Asian, Egyptian, and on the life and mobility of sperm; it has been sug- Greek cultures. Anaxagoras, a fifth century B.C. Greek gested that the androsperm (Y-bearing sperm) are philosopher, believed that semen from the right tes- stronger and faster but do not survive for very long. ticle produced sons, while semen from the left testi- Gynosperm, (X-bearing sperm), on the other hand, cle resulted in the birth of a daughter. Believing the are slower but have greater staying power, conse- same theory, men in the Balkans would squeeze the quently a longer life span (1). Intercourse position is right side of their scrotums in the hope of increasing also based on the mobility of sperm, with shallow pen- the odds of having a son. A misconception that per- etration (missionary position) favoring the concep- sisted till as late as the sixteenth century was that male tion of a baby girl, with deep penetration (rear entry) babies developed in the right side of the uterus. The favoring the conception of a baby boy (1). The Whelan Perfumed Garden, written by Shaikh Nefwazi, recom- Method is in complete disagreement with the Shettles mended turning the woman on her right side after the method and suggests the opposite (2). Whelan says man had ejaculated. The Charaka Samhita, a man- to have intercourse 4–6 days so as to conceive a ual written around 800 B.C. in India, advised prospec- boy before your basal body temperature goes up. tive parents who expressed a preference for sons that To conceive a girl, intercourse should occur 2–3 days they should “abstain from intercourse for a week, gaz- before ovulation. ing every morning and evening upon a majestic white In 1984, the World Health Organization published bull or stallion, being entertained by pleasant tales, a study that failed to confirm gender predominance and feeding their eyes on men and women of gentle when timing conception relative to ovulation (3). Un- looks.” Mistaking vaginal secretions for semen, an- terburger had made observations with respect to al- cient Greek, Hebrew, and Indian literature stated that kalinity and acidity and gender predetermination (4). both men and women produced semen. Sons were Women recommended to use an alkaline douche (for born when the male semen was predominant. Mas- overcoming fertility problems) conceived a higher turbation after a period of sexual abstinence usually than usual number of boys (4). results in the ejaculation of a greater amount of se- Langendoen and Proctor first published The Pre- men. Based on this observation, sexual abstinence was Conception Gender Diet in 1982, on the basis of re- recommended for men who wanted sons. An ancient sults reported by Stolkowski and Lorrain in 1980 (5). Chinese birth chart predicts sex of the child based on The theory is that by altering your diet to include and the age of the mother at conception and the month of exclude certain foods, the conditions in the reproduc- conception. This is followed by documented scientific tive tract will be directly affected, increasing the odds efforts beginning in the 1600s to sway the chances of of conceiving a particular sex. This theory is also con- achieving a pregnancy by a variety of methods. Re- sistent with the oriental philosophy that everything search and work carried out in the 1980s and 1990s has a yin or yang quality and the foods supplied in have finally provided methods offering the chance of the boy diet (boys and alkaline) are all yang and the Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
  • 3. The 50 Million Missing Women 413 foods supplied in the girl diet (girls and acid) are all ferent concentrations, and the Y and X sperm are be- yin. Claims of 80% accuracy, based on one clinical lieved to be partially separated at low speed inside a trial of only 260 women, the results were published in centrifuge by their differential sedimentation veloci- the International Journal of Gynaecology and Obstet- ties. The rationale to this treatment is that the X sperm rics in 1980 (5). The girl diet is high in calcium but low is believed to be bigger and heavier than the Y sperm in salt and potassium, containing acid-forming foods. and it will sediment down the Percoll gradient quicker The boy diet is high in salt and potassium but low in under centrifugation. If sperm collected at the bottom calcium and magnesium and contains alkali-forming of the Percoll gradient are used for artificial insemi- foods. nation, the chances for conceiving a girl should be The majority of the artificial sex selection meth- greater. ods work by separating X- and Y- bearing sperm and With the recent advent of Microsort (flow cytomet- require artificial insemination. The Ericsson Method ric separation of X and Y sperm) and preimplanta- was developed about 25 years ago and has been in clin- tion genetic diagnosis (PGD), couples no longer have ical use for the last 20 years. Currently, there are over an excuse to employ abortions to select sex. The Mi- 40 Sperm Centers using this procedure in the world, crosort method is an expensive approach to gender se- and over 2000 healthy babies have been born using lection involving the separation of the X sperm from the albumin treatment, the great majority of them in the Y sperm. This method uses a technique known the United States. as flow cytometry where seminal fluid is filtered and The treatment for conception of a boy involves run- then forced through a long, thin tube under pres- ning the husband’s sperm sample through columns sure. At the other end, the tube divides, and there containing human serum albumin solutions of differ- is a fluorescence-based switch, designed to direct the ent concentrations by which Y-bearing sperm can be larger X sperm into one direction, and the smaller separated through a filtering process (6). In January Y sperm into a different direction. The desired X-rich 1998, Hong Kong researchers who used the Ericsson or Y-rich sperm samples can then be used for artificial method (7) published a paper. They did DNA stud- insemination (11). ies on the supposedly X-rich and Y-rich samples pro- duced by the separation and found that each sample CULTURAL ISSUES still contained the original 50% ratio of X-bearing to Y-bearing sperm. Many have claimed success at this The problem with trying to prevent couples from type of sperm separation, but few have been able to aborting female fetuses is that cultural traditions die back up their claims with hard data. hard, and a particularly powerful one is that boys are There have been several reports in the scientific lit- infinitely more desirable than girls. The reason is sim- erature recently which suggest that sperm subjected ple: when parents marry off a daughter, society ex- to a swimup procedure and used for artificial insemi- pects them to give a huge dowry to the boy’s family. nation can increase the chances of conceiving a male This represents an enormous burden that often wipes by between 80 and 90%. In one study carried out in out a family’s entire savings. Recent advertisements 1993, 23 of 26 births were male claiming a success in the national press and on the internet extolling the rate of about 88.5% for male sex selection (8). Two “highly effective” gender selection kit marketed by a recent studies suggest that the Percoll density gra- U.S. company has created a hornet’s nest. The govern- dient method is effective in both separating the X ment is naturally perturbed about the ramifications and Y sperm and also skewing the birth sex ratio in of such advertisements and its potential to skew the humans (9,10). already-tilted female–male birth ratio in the country. A 1996 study suggested that bottom (X) fraction Recent editions of India Abroad, a weekly newspa- sperm, derived from the eight-layer discontinuous per for Indian expatriates in the United States and Percoll gradient, have higher motility, progression, Canada, are carrying sex preselection ads by compa- and hyperactivation when compared with top (Y) nies to promote their products to one of the country’s fraction sperm. The bottom (X) fraction sperm have fastest growing ethnic groups. And the target market greater longevity in motility and have shorter tails, is immigrants from India, where sex-determination supporting earlier hypotheses of sex differences in tests were outlawed 8 years ago in a still unsuccessful sperm parameters (9). In the Percoll procedure, the effort to thwart the widespread practice of aborting fe- sperm sample is layered on top of a Percoll density male fetuses. Such ads would be illegal in India, which gradient consisting of many layers of Percoll at dif- has struggled for years to discourage women from Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
  • 4. 414 Allahbadia exploiting medical technology to assure themselves ics, buoyed by record profits, are aggressively selling of giving birth to boys. Now, Indians in the United their wares. One clever economic pitch blares from States and Canada find themselves being courted by tens of thousands of billboards through the country— American companies that promise to help do just that. Pay five hundred rupees [US$14.00] now rather than In India and China, female infanticide is both so- five lakhs [Rs 500,000 or $14,000] later. Poor families, cially sanctioned and undeserving of mourning. Yet, fearing expensive dowries that can cripple a family, one should consider it repugnant to kill the fetus by willingly undergo the tests. Coming on top of more way of abortion, especially when only done to abort than a century of female infanticide in regions where a girl fetus. This would appear even more the case sons are preferred, medical technologies of amnio- in our country where women deities are worshipped centesis, ultrasound, and chorionic biopsy have com- in various forms. In both Karnataka and Bengal the pounded the problem of “missing females” over the deities of the state is a goddess. past two decades. Despite the 1994 Prenatal Diagnos- Few of India’s states show the political will to en- tic Techniques (Regulation and Prevention of Misuse) force the century-old law prohibiting female infan- Act in India and China’s Human Reproductive Tech- ticide. A ritual which originated amongst certain of nology Ordinance of 2000, sex determination for pur- Rajasthan’s tribal communities, the murder of the girl poses of aborting female fetuses is presently a highly infant, is morally cleansed by the reasoning that killing profitable medical industry. In India, the act is an “on- takes place before the ritual bath, 7–10 days after paper-only” law which has proven to be a toothless birth, which grants an infant “human status.” This is tiger in the face of blatant abuse by elements of the further upheld by superstitions maintaining that the medical fraternity. Some go so far as to suggest that act enhances the chance of the next born being the they are helping curb the population explosion. Oth- preferred son. ers defend their lucrative business, saying it offers The killing of the infants, when born with deformi- women a less barbaric means than female infanticide ties of face and limbs, soon after the birth, is a frequent of doing away with their daughters. Needless to say, occurrence in India. The culprits are the dais (tradi- not a single legal case has been registered in India tional birth attendants) and old ladies who attend to or China against those peddling their technological child birth in rural communities. They, in their own misogyny. way, protect the family from the financial expenses Not surprisingly, proselective abortion activists feel and social stigmas associated with bringing up such that selective abortion has several merits important a child in a country where a lack of social education for the good of the general Indian public. For exam- prevents these unfortunate infants from living a full ple, advocates argue that selective abortion is the an- life and rehabilitating them. The problem has taken swer to population control. Perhaps they feel that in monstrous proportions in just the past two decades. a country where families are willing to have child af- Prenatal techniques for sex determination were in- ter child until they have their desired number of sons troduced into India only in the early 1970s. Although and daughters, sex selective abortions would allow touted officially as an aid in reducing genetic defects, women to choose the makeup of their family while much of the Indian public has turned to these tests to keeping the family size small. Another argument in find out if “It’s a boy” or not. The effects of these de- terms of population control is that families should be velopments on sex ratio can be observed in every class balanced; selective abortions will allow families to bal- of the society. An awareness program going right to ance their desire for a daughter with one for a son. It’s the grass-roots level and effective deterrent punish- a gut-wrenching fact that in a patriarchal country like ment to doctors who flout the law may be a solution. India, where sons are prized and daughters devalued The proliferation, and increasingly reported abuse, in society for a variety of reasons, it is likely that cou- of prenatal testing has forced an impassioned debate ples will choose to abort only females. throughout India. Those fighting against the tests cite studies which suggest that a further skewing of the sex ratio may only make worse the status of women, with RECENT CHANGES an obvious negative impact on the whole nation. On the other hand, there is a great deal of public support In India, requests for medically assisted sex selec- in India from prosex selective abortion advocates who tion are very common; for example, one fertility clinic feel that these tools are helping families to cope with in Mumbai used to receive about 250–300 requests for intransigent problems, especially dowry. Health clin- Y-enrichment with intrauterine inseminations each Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
  • 5. The 50 Million Missing Women 415 year till the time the Prenatal Diagnosis Act was ex- in subsequent treatment cycles. This has advantages in tended in 2002 to include sex selection using sperm both reducing the cost of further treatment and min- separation techniques as well. Imprisonment for up to imizing greatly the number of unwanted embryos. 3 years is the deterrent used by the Union government Sex selection is controversial because it is the first against medical practitioners who continue to do sex example of genetic selection for a nondisease trait. determination tests. As I write this paper, the scenario Being a boy or a girl is not a disease. So should par- truly appears to change, and in 2002 the government ents be permitted to select traits other than the sex of seems serious and has really clamped down on clinics their children? Few aspects of human development offering sex selection or sex determination. Every ul- are more significant than one’s sex; it’s a central fact trasound machine manufacturer has to furnish a list of one’s identity as a human being. If it is ethically of the doctors to whom their units have been sold, permissible for parents to make that choice, the case and these doctors now have to compulsorily register for letting them make less significant genetic choices with the government and put up boards outside their for their offspring is already made. In an ethical state- clinics proclaiming that This clinic does not perform ment issued last year, the American Society for Re- any sex determination. productive Medicine concluded that if Preconcep- tional Sex Selection is found to be safe and effective, “physicians should be free to offer pre-conception PGD FOR SEX SELECTION gender selection in clinical settings to couples who are seeking gender variety in their offspring” (13). There is a very affluent trader community in Some others see the use of preimplantation sex se- India whose religious beliefs do not allow medical ter- lection as a slippery slope to eugenics, since the mination of pregnancy. It is this rich, male-oriented same techniques can be used to test for other genetic community that has spawned a whole new breed of traits. fertility clinics attempting to offer PGD-IVF for selec- They might want to ponder the story of 6-year-old tive transfer of male embryos. Each attempt of PGD- Molly Nash, who suffered from the fatal genetic dis- IVF for transfer of male embryos can cost as much ease, Fanconi anemia. The only cure for Molly’s dis- as US$5000 even in a “developing” country such as ease is a bone marrow transplant from a compatible India, where more than 50% of the populace lives be- donor. Her parents used preimplantation genetic test- low the poverty line. Sex selection may, therefore, be- ing to help them bear a sibling who would be a per- come more acceptable to some couples, and requests fect genetic match for her. Using IVF, Molly’s parents for clinics to provide it may become more common. produced 30 embryos that were tested for the dis- IVF techniques for gender selection began with ease gene and for transplant compatibility. Only five a single cell being removed from an eight-cell em- had the right genetic makeup. The fourth attempted bryo under the microscope. The cell was then ana- pregnancy resulted in the birth of Adam Nash in lyzed for genetic disorders and/or gender by FISH August 2000. His umbilical cord blood stem cells were (Fluorescence in situ hybridization). The FISH tech- used to replace Molly’s defective marrow, and now nique utilizes fluorescent probes which are specified both children are healthy. Few people would regard for chromosomes. This technique is used for sex de- what Molly’s parents did as immoral. After all, genetic termination and for structural chromosomal abnor- testing in this case resulted in two valued and healthy malities and allows to select only the chromosoma- children. lly normal embryos with the desired sex for embryo Therefore, I strongly believe that it is sometimes transfer (8). At the 8- or 16-cell stage, embryos can ethical to let parents choose their children’s sex. be sexed very reliably by removing one or two cells and sexing these with FISH or PCR methods (12). REFERENCES Once the genders of all the embryos have been de- termined, the embryos (normally between two and 1. Shettles LB: Letter: Sex selection. Am J Obstet Gynecol four are transferred depending on the woman’s age) 1976;124(4):441–442 of the desired sex are then replaced in the uterus. By 2. Daniell JF: Sex-selection procedures. J Reprod Med 1983;28(4):235–237 combining the IVF method with sperm sorting, using 3. World Health Organization: A prospective multi-centre Microsort technology, the number of male or female study of the ovulation method of Natural Family Planning embryos could be greatly enhanced, and those em- for the outcome of pregnancy. Fertil Steril 1984;41:593– bryos that are not replaced can be frozen and be used 598 Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002
  • 6. 416 Allahbadia 4. Gledhill BL: Gender preselection: Historical, technical, and on discontinuous Percoll gradient for sex preselection: Com- ethical perspectives. Semin Reprod Endocrinol 1988;6(4):385– puterized analyses. Arch Androl 1996;37(1):1–5 395 10. Wang JX, Flaherty SP, Matthews CD: Sperm separation for sex 5. Stolkowski J, Lorrain J: Preconceptional selection of fetal sex. selection. Hum Reprod 1998;13(9):2659–2661 Int J Gynaecol Obstet 1980;18(6):440–443 11. Fugger EF, Black SH, Keyvanfar K, Schulman JD: Births 6. Ericsson SA, Ericsson RJ: Sex ratio of male sex preselected of normal daughters after Microsort sperm separation and children born to couples with exclusively female offspring. intrauterine insemination, in-vitro fertilization, or intra- Arch Androl 1992;28(2):121–123 cytoplasmic sperm injection. Hum Reprod 1998;13:2367– 7. Rose GA, Wong A: Experiences in Hong Kong with the theory 2370 and practice of the albumin column method of sperm separa- 12. Sills ES, Goldschlag D, Levy DP, Davis OK, Rosenwaks Z: tion for sex selection. Hum Reprod 1998;13(1):146–149 Preimplantation genetic diagnosis: Considerations for use in 8. Check JH, Katsoff D: A prospective study to evaluate the ef- elective human embryo sex selection. J Assist Reprod Genet ficacy of modified swim-up preparation for male sex selection. 1999;16(10):509–511 Hum Reprod 1993;8(2):211–214 13. Ethics Committee of the American Society for Reproduc- 9. Watkins AM, Chan PJ, Patton WC, Jacobson JD, King A: tive Medicine. Preconception gender selection for non medical Sperm kinetics and morphology before and after fractionation reasons. Fertil Steril 2001;75(5):861–864 Journal of Assisted Reproduction and Genetics, Vol. 19, No. 9, September 2002