Reproduction and contraception are major life events; for adults, at least one of the two must be involved. Although people have spared no effort to invent and apply various contraceptive techniques in order to get rid of the reproductive function of sex and pursue sexual pleasure, another one in ten men and women who reach the age when they want to become parents are troubled by the fact that they cannot have children through the most primitive and natural way.
1. Conception
The female egg is derived from the germ cell during the embryonic period. There are about 2-3 million undeveloped primordial oocytes in the two ovaries of a baby girl at birth. When a girl has her first menstrual period, the dormant oocytes in the ovaries are awakened and develop into mature eggs that are expelled from the ovaries and enter the fallopian tubes. The egg is then released from the ovary and enters the fallopian tube, where it waits for the arrival of the sperm, but if it fails to do so, it withers away and the next menstrual cycle begins again. A woman goes through about 400-500 menstrual cycles, each with one mature egg, until she is completely menopausal after menopause. Some women can have two or more eggs at a time (medically called superovulation, which is related to endocrine hormones and is inherited), which happen to be fertilized at the same time, resulting in the birth of dizygotic twins or multiple births, such as the rare dragon and phoenix fetus, and two (or more) embryos that split from a single fertilized egg, which are identical twins.
Male infants are also born with primordial spermatogonia, and the sperm-producing testes remain in the abdominal cavity during the embryonic period and descend through the groin into the scrotum just before birth. However, about 3-10% of male infants are born with testicles that do not descend into the scrotum or descend incompletely, i.e., cryptorchidism; in the past, folklore used a simple method to pull off the incompletely descending testicles of young boys, commonly known as “egg pulling”, but there is nothing that can be done for testicles that are completely hidden in the abdominal cavity. -In modern times, the problem can be solved by surgery. Since the testicles will atrophy at a body temperature of 37 degrees, the earlier the surgery, the better, and not older than two years. After male puberty, the testes become a spermatogenic factory where spermatogonia grow rapidly into mature sperm and are in constant supply, producing approximately 100 million sperm per day, which is the order of magnitude needed to fertilize an egg. The best temperature for sperm maturation is 1 to 2 degrees below body temperature, if it is higher than 38 degrees, it will affect sperm vitality, so infertile men who like sauna should be careful, and usually do not use hot water above 37 degrees to soak their balls.
The sperm is a very important part of the process. The woman’s uterus has a sticky secretion that is prepared for the selection of strong sperm, those weak and weak sperm cannot pass through the cervical mucus, and the strong and healthy ones can enter the fallopian tubes. If there happens to be a pregnant egg in the oviduct, a group of sperm swoops in and surrounds the egg, the lucky one breaks through the egg’s cell membrane first and the nucleus of the sperm fuses with the egg’s nucleus to become a fertilized egg and begins to divide into multiple cells. On the seventh day after fertilization, the embryo, which is still a clump of cells, rolls around in the fallopian tube and rolls through the tubal fluid to the uterus, where the outer layer of differentiated placental cells adheres to the uterine wall and fuses with the warm and soft endometrial cells, anchoring the embryo in the uterus and establishing maternal-fetal circulation, a process also known as embryo implantation. After the embryo implantation is completed, the placenta develops rapidly and delivers nutrients to the fetus, which grows until it is delivered from the mother’s womb at 40 weeks.
2. Infertility
From the maturation of the egg and sperm to the formation of the fertilized egg and then to the implantation of the embryo, which is regulated by a variety of endocrine hormones and immune factors, is a complex, precise and long process, and any mistake in the process may lead to infertility.
In men, low sperm count, azoospermia, dead sperm, low sperm viability, low sperm vitality, etc., and in women, ovarian insufficiency (mostly endocrine abnormalities), non-ovulation, blocked fallopian tubes, irregular menstruation, amenorrhea, defective uterine development, and secretion of anti-sperm antibodies can lead to primary infertility (persistent inability to conceive). In addition, sexually transmitted diseases (e.g. gonorrhea, condyloma acuminatum, etc.) can lead to blockage, adhesions and restricted umbilical function of the fallopian tubes in women, and paraphimosis and obstructive azoospermia in men, which can cause secondary infertility (previously able to conceive and then unable to conceive again). Too many abortions or complications caused by abortion, such as incomplete abortions, reproductive tract infections, and ruptured ovarian cysts, may also lead to secondary infertility.
According to World Health Organization statistics, the incidence of infertility in developing countries is about 8-12%, with the primary infertility rate being 2-5% and secondary infertility being 10-33%, with environmental degradation and delayed reproductive age being the main factors leading to the increase in infertility. Boys and girls become fertile upon reaching puberty, but by the actual age of childbearing, it is more than a decade later. The current trend of premarital sex is unstoppable, yet many energetic young men and women know little about sex, contraception, and reproductive health. The high incidence of premarital sex and the low rate of reproductive health protection form a huge contrast, and I am afraid that this is one of the important factors for the increase of infertility. Therefore, I think that reproductive health education should start from children.
The development of science and technology always responds to people’s needs; the emergence of assisted reproduction technology brings hope to some men and women who are caught in the dilemma of infertility.
3.Artificial insemination
Artificial insemination refers to a method in which a man’s semen is collected and then injected into the female reproductive tract (uterus) by artificial means to replace sexual activity and make the woman pregnant. Artificial insemination is a relatively simple assisted reproduction technique and is only used in cases where the man is unable to ejaculate normally (e.g., supra-urethral cleft, hypospadias, stubborn insemination, severe premature ejaculation, reverse ejaculation, impotence, etc.) or where the woman’s cervix is narrow and the cervical mucus is excessively viscous so that sperm cannot pass through. Or for special reasons to have a child by non-coital means, such as the heroine in the movie “Left and Right” who tries to have another child with her ex-husband by artificial insemination.
In addition, artificial insemination technology is widely used in animal breeding (e.g. meat pigs and broilers), livestock breeding (e.g. high quality dairy cows), and breeding rare animals (e.g. giant pandas and northeast tigers).
4.In vitro fertilization
For patients with abnormal ovulation in women and sperm defects in men, they need to resort to IVF technology.
IVF technology in English is In Vitro Fertility (IVF for short), or in vitro fertilization. Although in vitro fertilization literally sounds similar to artificial insemination, there is a fundamental difference. In vitro fertilization involves removing the male sperm and the female egg from the body and allowing the sperm and egg to unite under in vitro culture conditions to complete the fertilization process, but this is only applicable to couples with normal male sperm; in cases where the male sperm is defective and the sperm cannot fuse into the egg cell on its own, the nucleus of the sperm needs to be injected into the egg cell through microinjection. The fertilized egg begins to divide and is cultured in vitro for 2 to 3 days before developing into a blastocyst (early embryo), which is then transferred into the woman’s uterus. However, conception is not complete until the placental cells that surround the periphery of the embryo are able to implant in the uterine wall and establish maternal-fetal circulation. The name IVF is derived from the fact that the union of the sperm and egg and the initial embryonic development take place in a “test tube”.
The first IVF was performed in 1978 by Edwards, a British embryologist, in collaboration with Dr. Steptoe, an obstetrician and gynecologist, and is now 30 years old. IVF technology is now well established and its average success rate (live birth rate) is around 30-40%, but the conception rate (the percentage of in vitro cultured blastocysts that successfully implant in the uterine wall after transfer to the uterus) is clearly related to the age of the woman. In general, women under 30 years of age have a success rate of more than 50%, while only about 11% of women over 40 years of age are able to conceive. This shows that regardless of the method of conception, it is an unbreakable truth that “it is important to have a baby before it is too late”.
5. Gestational Surrogacy
Although IVF can give women with infertile ovaries the hope of motherhood, there is nothing that can be done for women with infertile uterus. Congenital uterine development defects, spontaneous miscarriages (also called habitual miscarriages – as an aside, although multiple abortions may lead to habitual miscarriages, many women who have never had an abortion will also have symptoms of habitual miscarriages, which are immune or endocrine disorders, so for male readers, don’t feel free to doubt your girlfriend’s or wife’s history because of this), or due to medical conditions. In addition, women with intrauterine growth restriction and severe hyperemesis also have difficulty having a healthy child. This is a great pain and regret for women with normal ovaries but infertile uterus, which is why Gestational Surrogacy was created.
Gestational Surrogacy is not the same as the traditional “borrowed child”. The process of gestational surrogacy is similar to in vitro fertilization, in which sperm and eggs are removed from the entrusted couple, fertilized and cultured in vitro, and a blastocyst is implanted in the womb of the surrogate mother; the fetus develops and grows in the womb of the unrelated surrogate mother, and is returned to the genetic parents when it falls to the ground. Traditionally, the husband provides the sperm and the surrogate mother provides the egg, and the child is the surrogate mother’s own flesh and blood; before assisted reproductive technology, the only way to get a child was to have the husband sleep with the surrogate mother, but now it is possible to use non-coital methods such as artificial insemination or in vitro fertilization (see, this is the power of science). ).
The world’s first gestational surrogate was born in 1985 in the U.S. In 2005, the American Fertility Association conducted a statistical survey of more than 3,000 gestational surrogacy cases nationwide from 1993 to 2002, which showed that the success rate (live birth rate) of gestational surrogacy was 39.3%, indicating that gestational surrogacy is a relatively mature and established practice. surrogacy is a relatively mature and safe assisted reproductive technology (here). The recent news story “American lesbian couple gave birth to twins on the same day”, which has been reprinted by major online media in China, is the result of IVF and gestational surrogacy technology (see English news here). Interestingly, both sets of twins actually came from the in vitro fertilization of one mother’s eggs with donor sperm, and the doctors implanted four in vitro cultured embryos into each mother’s uterus, so one was a genetic mother and the other was a gestational surrogate, and the births were actually quadruplets in the genetic sense.
Commercial surrogacy is currently prohibited in many countries, such as the UK, Japan, Canada and New Zealand, but non-profit surrogacy is legal (i.e. it requires surrogate volunteers and, like bone marrow donation and organ donation, cannot be sold or contracted commercially); in some US states, the Netherlands, Belgium and other countries, commercial surrogacy is a legal business. The Measures for the Administration of Human Assisted Reproductive Technology promulgated by the Chinese Ministry of Health in 2001 explicitly prohibits “any form of surrogacy technology”, so don’t look at the various surrogacy websites and surrogacy companies on the Chinese Internet nowadays, but they are actually illegal agencies.
6.Womb transplantation
Although finding a surrogate mother is an option for women with infertile uterus, there are many legal, ethical and economic issues involved. In addition, many women with infertile uterus would like to be the gestational mother of their own children and experience the sweetness and sourness of pregnancy, and uterine transplantation has become another new way to solve this problem.
In 2002, a 26-year-old woman in Saudi Arabia who had her uterus removed due to a hemorrhage during childbirth several years earlier underwent a uterine transplant, but had to have her uterus removed again more than three months later when a blood clot occurred (here). In 2003, scientists improved the transplantation technique and gave birth to healthy mice from allografted wombs (here). However, some experts say that it is better to test on primates first before doing it, because generally patients after allograft surgery need to take anti-immune rejection drugs, and most of these drugs have serious toxic effects on the fetus (here).
7. Outlook
Recently, Nature News did an interview on IVF technology (Making babies: the next 30 years), including experts in IVF, stem cells, genetics, and more. In the article, the first Singaporean reproductive scientist has the audacity to imagine that 100-year-olds will have babies, artificial placentas, in vitro batch production of mature human embryos, and more. However, this expert’s idea of induced differentiation of pluripotent stem cells from the skin to obtain reproductive stem cells is an interesting idea. endocrine function to maintain a pregnancy).
The cost of IVF technology is still high, about 50,000 to 150,000 RMB in China and about $10,000 in the U.S. However, as the technology matures and costs decrease, it is expected to be cheaper in the coming decades.