State of art of infertility treatment

By Prof Oladapo Ashiru, MBBS, MS, PhD, HCLD/CC. FASN, OFR
University of Illinois at Chicago, US 

Louise Brown, the first baby born through IVF technology clocked 40 years in July, 2020. I am, therefore, writing this article to focus on this extraordinary technique that has saved many lives and has been used to birth almost seven million babies. IVF has also saved several broken homes and brought happiness to many families. In Nigeria, our journey into IVF started almost 40 years ago through landmark scientific research by Ashiru followed by applied clinical research and skill by Ashiru and Giwa-Osagie, leading to the first test-tube baby in Nigeria and Western Africa in 1989. Others join the race and as of today, there are over 60 clinics that are members of the Association of Fertility and Reproductive Health in Nigeria.

The IVF of 40 years ago has evolved significantly

At a recent meeting in Copenhagen, the World Health Organisation had experts from different regions to consider the formation of a multinational registry on Assisted Reproductive Technology. One of the issues that came out of this meeting and that of an earlier one in Geneva at the WHO headquarters was ‘‘infertility is a human right issue.’’ Hence, everything must be done to allow everyone have access to fertility care.

Infertility is the inability to get pregnant after a year of unprotected intercourse. About 10 per cent of couples in the United States of America are affected by infertility. Both men and women can be infertile. According to the Centers for Disease Control, one-third of the time the diagnosis is due to female infertility, one-third of the time it is linked to male infertility, and the remaining cases of infertility are due to a combination of factors from both partners. For approximately 20 per cent of couples, the cause cannot be determined (unexplained infertility). Consequently, the WHO meeting has now made clear definitions for male infertility and female infertility distinct from each other.

There is a worldwide emotional epidemic of infertility. As of today, twenty-five percent of couples are infertile. Even in India which has severe overpopulation, the most common reason for a visit to the doctor is infertility. In Nigeria, infertility which used to be a small area of gynaecology practice has now become a huge discipline with several doctors devoting their clinic solely to the practice of infertility. During the conference of the Nigerian Association of Fertility and Reproductive Health and the African Fertility Society on September 24, 2015, the number of IVF clinics in Nigeria was close to 50. The number of IVF clinics in Africa is near 150, and in comparison, the number of clinics in Chicago city alone is over 60! It is clear that Nigeria is now recognised worldwide as part of Assisted Reproductive Technology providers. It is noteworthy that many countries still do not have the ability to provide ART services.

The human ability to get pregnant decreases with age, which explains why only one per cent of teenagers are infertile while a large majority of infertile couples are in their thirties. It is well documented that from our teen years when the last thing we want is a child, to our mid-thirties when we are finally secure enough to start our family, our ability to conceive decreases almost by twenty-five per cent.

Research shows that in the past 30 years, infertility has increased and those over the age of 30 have the most problems.

If you are in your thirties and have been working to establish yourself in your profession, and are now just casually reading this column because you are thinking maybe in a few years I might like to start a family, you should realise that there is a 25 per cent chance you will not be able to do so without medical intervention. It is for this reason that the definition of infertility was made to include a person of age 35 years who has not been able to achieve pregnancy within six months of attempt at conception.

Other factors that may make it difficult for you to get pregnant include abnormal organs, immunological factors and other malfunctioning of the body system. The dramatic increases in infertility over the last 30 years has been blamed on various factors including the increases in sexually transmitted diseases, environmental toxins in our food such as heavy metals in fish, environmental pollution particularly in the oil-producing geographical zones, declining sperm counts from absorption of toxic substances and even the increased tension and anxiety of the modern life.

In all other animals except humans, the desire to have sexual intercourse is timed to correspond exactly to that moment when the female is ovulating or producing eggs that can be fertilised. Take, for instance, a dog or a rabbit, once the female is ovulating she seeks out the male and after intercourse, the female is usually pregnant with multiple pregnancies. Humans, however, desire to have sex at any time regardless of whether there is an egg that can be fertilised in the woman and it makes us reproductively more inefficient than other animals.

We know that in all species, there is a very short window, in fact, a matter of days during each month that the female is fertile and can get pregnant with intercourse. The timing of sex is therefore very important if a species is to have an efficient and high fertility rate.

In humans, women go through a period of fourteen days when the follicle in the ovary develops. This starts from the day one of the menstruation until the egg is sufficiently matured and ready for ovulation. Once the egg is released at ovulation, there is another fourteen days period that it can be fertilised. If intercourse occurs at the right time, then the embryo grows and implants in the uterus, or womb. If intercourse occurs at another time other than the ovulating period, it is very unlikely that the woman will get pregnant in that cycle /month.

Animals go through what is described as an ‘estrus’ cycle or ‘heat.’ Humans go through a menstrual cycle. Apart from other hormonal variations, one significant difference between humans and animals is that the female sex hormone, oestrogen, which increases just before ovulation in animals is the trigger factor for their sex drive. This hormone is responsible for producing eggs. In other words, animals do not desire to have sex unless there is an egg to be fertilised in the female’s womb. In humans, sex desire is much more complex and is not driven by the female sex hormone oestrogen, but by the male sex hormone testosterone. This is unique in the animal kingdom and it is a human phenomenon. The small amount of testosterone that the female makes are enough to generate a sexual drive in her. It is only few females that recognise the slight increase in testosterone around the ovulation period to enable them to deliberately initiate sex at the appropriate time to get pregnant.

From sociological studies, the fact that humans make love facing each other indicates a communication of direct sexual interest and development of love, permanent mating and a family system. On the contrary, throughout the animal kingdom, the female squats in her position of ‘heat’ and the male mounts on top of her, facing her rear end. The animals never get to look at each other and do not need to know each other or get emotionally involved for intercourse to take place. In other words, in animals, sex is not emotional but procreational. For humans, having sex is about expressing emotions and not just for the purpose of having babies. This makes us less reproductively efficient which makes infertility common in humans because the human reproductive system was never that efficient to begin with.

The reproductive system of the human male is also highly inefficient. Most male animals produce 25 million sperms per day per gramme of testicular tissue. Humans produce only four million sperms. Only the gorilla, the cheetah and the goose produce less sperm per gramme and testicular tissue than humans.

To illustrate the importance of sperm per gramme of testicular tissue, the average bull ejaculates about ten billion sperms whereas the average fertile man ejaculation would contain between one and five million sperms. This means that the average bull in a single ejaculation produces thirty to one hundred times more than that of the average man. The bull sperm will also move three times the speed of the human sperm, in a perfectly straight line, with virtually no abnormal, weak or deformed sperms. A man whose ejaculation has 60 per cent of the sperm moving is lucky. Studies on sperm population find that up to 40 per cent of a man’s sperm are abnormal.

The pig as an example also really shows superior fertility. The pig ejaculates an entire pint of sperm on having sex with the sow. Its’ orgasm will take a full half-hour. Compare this to a mere 120 seconds (2 minutes) for most men. Also, the pig has little screw-like grooves on the end of its penis that fit into a similar groove in the cervix of the female. This guarantees that no sperm will leak during intercourse. The amount of sperm in a single pig’s ejaculation is about four hundred times higher than the amount of sperm in a single human’s ejaculation, and none is lost. In most animals, the sperm cells as they mature from stage to stage, are arranged in perfect order. This is not so in humans whose sperm cells mature in a helter-skelter fashion according to histologists.

Why is human sperm count so poor?

Several factors have been blamed for the low sperm count in men.

Stress: It has been well documented that modern life can have a negative impact on reproduction. Many sperm banks in Europe, America and here in Lagos get medical students or other professional students to donate their sperms. It is not unusual for good donors with high sperm counts on one occasion to have a poor sperm count on the next occasion. There was a case in the University of California, United States of America where a donor’s sperm count went literally zero. It was only a close interview that revealed that this student was going through a bout of depression thinking that his life was falling apart. There are cases of infertility with a low sperm count from the husband. When the couple goes on vacation, the wife gets pregnant because of the change in the environment, which may eliminate the male stress factor and improve the chances at conception.

Hazardous substances: There are several factors in the environment that have a terrible effect on sperm. To make the situation worse, many of these substances have not been thoroughly documented, researched or accounted for. In a village in China, for instance, in the early 1920s they discovered that fertility was on the decline and the women were not getting pregnant. Suddenly in the 1930s the sterility was reversed and the people started having children again.

The villagers thought that the curse placed on them had been lifted. It was later they realized that the sterility was due to a change in cooking oil. The use of cheap crude cottonseed oil for cooking created sterility in men.

It was found that the crude extract has a chemical called gossypols that causes male sterility and has now been used as a male contraceptive. A good number of these have been discovered by accident while there are several out there that are yet to be discovered.

There are possibly many herbs or fruits that contain gossypol-like substances that the Nigerian population eats and we do not know about. A lot of food intolerances have been found to lead to intestinal auto-intoxication that end up with toxins in the testis.

The same goes for food containing heavy metals. This is why proper medical detoxification is now a recommended part of infertility.

This article, from inception, has focused on In vitro fertilisation, an extraordinary technique that has saved many lives and has been used to birth almost seven million babies.

Some factors were listed in the previous article to contribute to low sperm count in men. Other factors are;

Sexually Transmitted Diseases: Research shows that about 10 per cent of human infertility is caused by tubule obstruction, and this is usually, although not always, caused by infectious diseases transmitted sexually. One-third of African men are sterile because of epididymal obstruction caused by sexually transmitted diseases. For example, gonorrhea causes irreversible tubule blockage. This type of infertility caused by sexually transmitted diseases requires the most complex medical treatment, which includes new methods of assisted conception or reproductive technology.

Obesity and Infertility

WHO now recommends that persons that are overweight or obese should lose at least five per cent of their body weight using lifestyle changes such as dietary or health spa/detox clinics before attempting conception.

Human destiny and fertility: 25 per cent of infertility are partly due to some of the reasons given above. The remaining couples suffering from infertility that cannot be explained need not be pessimistic. The new infertility technologies of IVF, GIFT, ICSI, microsurgery with TESA, and most recently pre-implantation genetic diagnosis can help most if not all infertile couples conceive.

What is the state of art in infertility treatment?

This refers to the process of solving seemingly impossible or difficult infertility problems with new technology. Such technology usually involves the complex handling of human gametes consisting of the sperm and egg in order to achieve conception and subsequent pregnancy, leading to the delivery of a healthy baby. In the United States of America, after the initial errors in California (by a Dr. Ricardo Ash) in which gametes were improperly handled, resulting in a black couple giving birth to a white baby while a white couple giving birth to a black baby, mandatory training and examination was stipulated and required before someone could be appointed the director of an IVF programme or laboratory. They must be licensed by examination as High Complexity Clinical Laboratory Director by the American Board of Bio-analysis. These individuals have helped in maintaining the practice of Assisted Reproductive Technology in the USA. The Copenhagen meeting under WHO watch now wants all practitioners of ART to start a registry of ART procedures through their national and regional fertility societies and then turn in to a multinational registry with WHO. This is to have a global picture of activities of ART worldwide for the purpose of funding, research, guidelines and regulations.

What type of infertility problem can be helped with the new technology?

There are several problems that can be helped with the new technology. They can be considered as those with male, female or even unexplained infertility.

Male infertility problems

Low sperm count and also a congenital absence of the sperm duct can be helped by the new technology. In this situation, men who were born with missing sperm ducts, today, are now able to have children of their own by ART procedure.

Female infertility problems

Anovulation

This occurs in 10 per cent of most cases of infertility. This female may go through a menstrual cycle but she is not ovulating, that is, not producing eggs. The process of ovulation is complex and involves secretions of several hormones in the brain, hypothalamus, pituitary and the ovary as well as other related endocrine glands like the thyroid gland, adrenal, pancreas and parathyroid. These endocrine glands secrete hormones, which work like the orchestra in a symposium to cause ovulation. If any of these hormones should play out of tune, ovulation will not occur. It is now possible to control this process externally by administering various hormones to the patient. This is done after a very careful analysis of the patients’ hormonal status and deficiencies.

 Tubal blockage

The tubes that carry the egg to the site of fertilisation may be blocked or restricted in their movement. This may result in failure to conceive, even though the patient may be ovulating normally. Blocked tubes occur in about 20 per cent of infertility cases. The cause is usually from previous infections. Sometimes, the woman may not know she had these infections. Even simple appendicitis when young can lead to scarring around the area of the tube which can interfere with the pickup mechanism of the eggs from the ovary. An X-ray called “hysterosalphinogram”  (HSG) which is a slightly painful but non-surgical procedure, which does not require hospitalisation can determine if the tubes are structurally sound. Most recently, there is a virtually painless procedure that is able to determine whether the tube is structurally intact. It is the use of ultrasonography with saline infusion. It is called Hysterosonography.

Immunology

This includes cervical hostility. In this situation, the woman’s cervix recognises the sperm as a hostile foreign body(antigen) and immediately produces antibodies to kill the sperm. Invariably, most of the sperm cells are destroyed just at the cervical entrance and do not pass beyond the cervix.

This condition can be detected by examining a swab of the sperm removed from the cervix after intercourse. It is called Post Coital Cervical Sperm Analysis. There are a number of other immunological factors that can affect pregnancy, conception to the implantation of embryo phase.

 The new technologies

Assisted Reproductive Technology as useful as it has been proven, is not necessary for every couple. A proper evaluation should be conducted by the specialist to ensure that the most efficient and cost-effective procedure is used to help the couple become pregnant. Each individual is different.

Assisted reproduction

Assisted Reproductive Technologies has now gone beyond in vitro fertilisation and intracytoplasmic sperm injection. A number of clinics render these support services in Nigeria.

Patient preparation and counseling

Good fertility clinics recognise that dealing with infertility or high-risk pregnancy can be very stressful. Patient preparation and counseling services were established to provide a range of mental health services to patients needing emotional support and guidance during difficult times. It includes a thorough evaluation of a detailed questionnaire, which has been prepared to bring all the possible factors that could cause infertility in couples. Patients are made to realise that they are not alone in their journey to parenthood.

Professor Oladapo Ashiru is the President of the Africa Fertility Society, Nigeria. He pioneered the IVF program in Nigeria and has over 25 years in the management of difficult cases of infertility, 15 years’ experience with ICSI and new assisted reproduction technologies.

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