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Review Article
Indian J Med Res 148 (Supplement), December 2018, pp 10-14
DOI: 10.4103/ijmr.IJMR_636_18
Infertility & assisted reproduction: A historical & modern scientific
perspective
Radhey Shyam Sharma1, Richa Saxena1 & Rajeev Singh2
1
Division of Reproductive Biology, Maternal & Child Health, Indian Council of Medical Research, New Delhi &
2
Department of Environmental Studies, Satyawati College, University of Delhi, Delhi, India
Received March 30, 2018
Infertility has always been considered as a social stigma and has often been treated as socially,
mentally and physically damaging experience for the childless women rather than man. Fatherhood
was more a social rather than biological concept, thereby making childlessness a legitimate ground
for divorce and a matter of disgrace for women. Every country has its own set of customs and
traditional beliefs for the relief of childlessness. While introducing a second wife was one way to
overcome the predicament of childlessness, divorce was also an available choice. There were several
myths that contemplated the human concerns and their needs during ancient times. It is evident
that types of the infertility and their treatment in the modern era have some historical background
and different representations in the ancient civilizations. The present review discusses the historical
and modern perspectives of infertility and assisted reproduction and their importance in different
cultures.
Key words Assisted reproductive technology - childlessness - cryopreservation - culture - fecundity - fertilization - history -
in vitro fertilization - infertility - surrogacy
Introduction Reproduction is unique in many ways, and it
performs a very important role in the process of
Affirmations from the present day modern science
immortality. Inability to have children, in general, is
managing cells, molecules, genes, DNA and on considered as a personal failure and tragedy around the
assessing ancient Indian Vedic literature, it appears world. The infertility does not end the life of a person
that parenthood is an instinct-driven physiological but it incurs wrecking impact on the life of that person
experience1-3. It is also evident that there is inherent for not full filling the biological role of parenthood.
and deep-seated desire in all adult females to have a The historical perspective and modern scientific
child. Instinct of parenthood is the most powerful knowledge described the intricacy of infertility, and in
desire that exists in all the living beings that include all this review, efforts have been made to highlight these
the creatures and people1-3. intricacies.
© 2019 Indian Journal of Medical Research, published by Wolters Kluwer - Medknow for Director-General, Indian Council of Medical Research
10
SHARMA et al: INFERTILITY & ASSISTED REPRODUCTION 11
Historical perspective Modern scientific perspective
The ancient era (3500 BC-500 AD) 4,5
The extension of the Middle Ages to modern
history was the Renaissance period, during which the
This era marks the beginning of the advancement of
scientific progress was made in the field of modern
civilizations from Indus Valley to Vedic Civilizations.
medicine including the infertility treatment. The
During this period, the tradition of Niyoga pratha or
practice of modern medicine originated in Greece
Levirate6 was prevalent to produce the child. It was
about 7th century B.C. Ancient Greeks believed in the
also evident from the Vedic literature that the general
conventional methods of treatment that were based on
population during that time was familiar with the idea
the religion, magic and superstitions; eventually after
of artificial insemination (AI) which involved the the beginning of medical science, the physicians and
manual injection of semen into the reproductive tract of surgeons disregarded the time-honoured elements of
the women7. Enchantment mixtures (‘Magic potions’) superstition and magic and were more in favour of
created by the sages for the queen of childless kings the factual medicine16. Later on, the famous physician
to make them pregnant was a typical practice during Hippocrates evolved a system of scientific reasoning
this era7. Thus, the people during that time were aware based totally on rational thinking17. Infertility was
about the ideas of assisted conception and gamete recognized as a medical problem requiring diagnosis
manipulation8. and treatment. Hippocrates during that time had
The common era (c.300 CE-c.400C)4,5 formulated various treatment options for the infertile
couples. While treatment in modern medicine focuses
During this time, bareness was typically presented more on pharmacological and surgical procedures,
as a problem for women. It was considered as a tragedy Hippocratic therapies were primarily based on lifestyle
for a woman in the ancient east since the barren wife changes.
was likely to be despised by her husband, family and
society9. The value of the women during Common The development of techniques for the treatment
Era was determined by her purity and after marriage of infertility can be traced back to the period when
by her reproducibility10. Although the introduction of physicians began to think scientifically about the
a second wife was a way of avoiding childlessness, reasons of infertility. In 1677, Antonie Philips van
divorce was also an option. In the Common Era, the Leeuwenhoek18 first discovered spermatozoa through
marriage agreement was thought to be completed not microscope. He named them as animalcules and
at consummation but with child birth11. One of the claimed their importance in the formation of embryos.
major causes of divorce during that time was women’s After the discovery of spermatozoa, advancements
infertility; as mentioned in majority of the Egyptian were made in modern medicine to understand the
marriage contracts, polygamy was very common and reproductive physiology, process of gamete interaction
the reason for a man opting for more than one wife12. and to treat and resolve infertility problems19.
The medieval period to the middle ages (ca. 500-1500)4,5 Evolution of infertility treatment
The suffering of women for not bearing the child Artificial insemination
continued from the medieval period to middle ages. In 1779, the essentiality of spermatozoa for
Wide range of religious views on infertility, existed fertilization was demonstrated by an Italian priest
from the late medieval period to the middles ages and physiologist named Lazzaro Spallanzani who
where the concepts of gender equality came into proved that a spermatozoon contained a nucleus and
existence; the necessity of procreation was understood cytoplasm through a laboratory experiment16. It was
as important carrier of lineage ahead for the continuity established for the first time that the embryo develops
and extension of the family13. Although religious as a result of physical contact between the egg and
discourse about infertility in those times focused the sperm20. With this new discovery, Spallanzani
mainly on women, men also were considered as culprits successfully inseminated dogs21. He also performed
for not producing the child. Polygamous marriage was an experiment to show that the spermatozoa could be
an ancient and long-standing solution to infertility in inactivated by cooling and reactivated later22. Another
the Middle East. Sometimes, the spouse was sought important discovery was that of Carl Ernst Von
to make a temporary alliance only for the purpose of Baer who in 1827 discovered the mammalian ovum
obtaining a child from them14,15. and made significant contribution to embryology16.
12 INDIAN J MED RES, DECEMBER (SUPPL.) 2018
Pioneering efforts by Ivanow (1922)23 to establish AI techniques were developed and intrauterine
as a practical procedure had begun in Russia. This insemination became popular, being more safe and
development by Ivanow led to further advancement painless. During 1920-1930s, the role of hormones
in the techniques and stimulated research outside in reproduction and conception was substantially
Russia to other western countries23. But while the AI examined; this led to the use of synthetic hormone
of animals quickly became an industry, it took several substitutes in the 1940s which today form an essential
years to use this technology to humans. Eleven years part of all infertility treatments. The history of early
after Spallanzani’s experiment, the first successful attempts of IVF dates back to 1890 when Prof. Walter
attempt of AI was made in a woman. First documented Heape reported the first case of embryo transplantation
report of application of AI was by a Scottish surgeon in rabbits in Cambridge university31. By the end of the
Dr John Hunter in late 1770s24. The real beginning 18th century, the concepts of reproduction became clear
of assisted reproductive technology (ART) started and fertilization was described as the fusion of nuclei
almost a century later when the first report on human of male sperm and the female egg32, and embryo thus
AI was published by Guttmacher (1943)25. Since created in vitro laid a significant milestone due to its
then, AIs have been reported for many years only in potential ability to progress to blastocyst stage, getting
cases of physiological and psychological dysfunction. implanted and be carried out to full-term gestation.
Around 190926, donor insemination - another aspect Around 80 years, later Robert G. Edwards and Patrick
of AI gained popularity. While the procedure of AI Steptoe performed the successful IVF in human leading
was gaining popularity throughout the world, in India to birth of Louise Joy Brown, the first test tube baby on
Sampat Kumaran reported the first AI in Halliker cows July 25, 197833.
at Palace Dairy Farm Mysore in 193927.
In vitro fertilization - The Indian scenario
Concept of cryopreservation
The history of IVF in India for infertility
The continued development in the field of AI treatments has come a long way. Just 69 days after
provided impetus for improved methods of collection the birth of Louise Brown, Dr. Subhas Mukherjee
of semen and its preservation. The development in the - an Indian scientist from Kolkata announced the
cryopreservation protocols for future use culminating birth of Kanupriya alias Durga following an IVF
into the modern techniques of sperm preservation procedure using cryopreserved embryo on October 3,
was a natural outcome of the progression of AI. Until 1978, world’s second and India’s first test tube baby.
mid 1800s, the efforts to actually freeze sperm did Unfortunately, his work could not be published in
not start. Later in 186628, Mantegazza became the the absence of scientific evidence. The detailed work
first to visualize the need of banks for frozen human of Subhash Mukherjee was later submitted in the
sperm. Around 150 years later, when the servicemen form of a report to the Government of West Bengal,
who were capable and without a doubt opted to freeze India, his significant work in IVF was also presented
and store specimens of their sperm before leaving for at the Indian Science Congress in 1978 and was also
battle during the Gulf war crises in 199229, the vision published in 197834. Dr Mukherjee developed novel
of Mantegazza’s turned into reality. The substantial and relatively unknown techniques at that time such
groundwork of Polge with glycerol laid the foundation as use of gonadotropins for ovarian stimulation,
for the cryopreservation of human sperm30. In 1953, cryopreservation techniques, freezing, storing and
Sherman froze human sperms using glycerol with slow thawing the embryos35,36.
cooling of sperm and dry ice as refrigerant. He further
established that on thawing of frozen sperm samples, In 1982, the Indian Council of Medical Research
the thawed sperm retained their fertilizing potential (ICMR) a pioneering Indian organization in the field
and induced normal development of the egg24 which of Biomedical Sciences took initiative realizing the
led to the first successful human pregnancy with frozen importance of treatment of infertility and initiated a
sperm. As a result of these improvements, the concept project (led by T.C. Anand Kumar and Indira Hinduja)
of sperm banking came into existence. at its Institute for Research in Reproduction (now
ICMR-National Institute for Research in Reproductive
In vitro fertilization (IVF) revolution
Health) at Mumbai. As a result, India’s first fully
The upsurge from AI to IVF was a massive one, scientifically documented test tube baby, ‘Harsha’,
both experimentally and publically. Semen preparation was born on August 6, 198637. Due to ever increasing
SHARMA et al: INFERTILITY & ASSISTED REPRODUCTION 13
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For correspondence: Dr Radhey Shyam Sharma, Division of Reproductive Biology, Maternal & Child Health, Indian Council of
Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, New Delhi 110 029, India
e-mail: [email protected]
