The only cemented constant in this world of probables. The healthcare landscape in Pakistan is everchanging and has been subjected to the same aforementioned oxymoronic phenomenon. There are so many challenges that come up unannounced. Some familiar, some not so much. But in our pursuit to tackle them, we can either keep up with the advancements and gallops in modern medicine or resort to the same herbs and spices for treatment as our uneducated forefathers did. Fascinatingly enough, the choice is not as clear as it might seem as for the most of our people. The modern Pakistani has to reconcile with far more health considerations in comparison to the Pakistani of the past whose biggest concern was finding a lady doctor for delivery. An issue that we can’t turn a blind eye to in this country is that of infertility, with conservative estimates pointing to around 17% of couples being afflicted with this misfortune of infertility. A beacon of hope for couples inflicted with this unfortunate condition is in-vitro Fertilization: a complex series of procedures that treat fertility, genetic problems and aid in conception.
Conventional IVF is just one of the many options available under the flag of assisted reproductive technology (ART). Assisted reproductive technology (ART) constitutes medical procedures which are used primarily to address infertility. When used to address infertility, it may also be referred to as fertility treatment. ART mainly belongs to the field of reproductive endocrinology and infertility. Some forms of ART are also used with regard to fertile couples for genetic reasons (preimplantation genetic diagnosis). ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART. Other than conventional IVF, the other viable options include:
i) Intra-Uterine Insemination (IUI): It is a fertility treatment that involves placing sperm inside a woman’s uterus to facilitate fertilization. The goal of IUI is to increase the number of sperms that reach the fallopian tubes and subsequently increase the chance of fertilization. It is used primarily in the cases of idiopathic infertility.
ii) Intra-Cytoplasmic Sperm Injection (ICSI): Intracytoplasmic sperm injection is an in vitro fertilization procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embryos that may be transferred to a maternal uterus. It is usually considered in cases of severe male infertility. It is used foremostly after IVF has proven to be unsuccessful.
iii) Intra-Cytoplasmic Morphological Sperm Injection (IMSI): The intracytoplasmic morphologically selected sperm injection (IMSI) is a laboratory technique used for In Vitro Fertilization treatments and involves inserting morphologically selected sperm into the egg. A prior sperm sorting is conducted and those with abnormalities that could hinder pregnancy are discarded. This treatment is considered for males with an abnormally low sperm count.
iv) Minimal Stimulation IVF: Minimal stimulation IVF is a relatively new ART technique in the United States that offers a gentler version of ovarian stimulation compared to traditional In Vitro Fertilization. It involves the administration of less potent fertility drugs to increase the chances of conception. Low Stimulation IVF allows patients at risk of Hyperstimulation to reduce the chances of multiple births, beginning with the lowest drug doses possible.
v) Natural Cycle IVF: Natural cycle IVF is a treatment similar to traditional, or stimulated, IVF, but without the use of medications to stimulate the ovaries to produce multiple eggs. It might sound appealing to those who dislike medications. The problem, though, is that these ‘natural cycles’ still require all the other costly and demanding aspects of traditional IVF. The frequent appointments, injections to trigger ovulation, surgical egg retrievals, and embryo development in the lab are all present in natural cycle IVF. Yet, this treatment has unequivocally demonstrated a significantly lower rate of pregnancy than traditional IVF.
IVF is rudimentarily a process of fertilization where an egg is combined with sperm outside the body, in vitro (in glass). The underlying principle of IVF revolves primarily around ovulation induction, which essentially involves taking fertility medications for months to help a patient’s ovaries produce eggs that are suitable for fertilization. The next step in the process is a minor surgical procedure that involves egg retrieval, where a medical professional extracts eggs from the patient’s ovaries. Once that is successfully done, the eggs are mixed with sperm cells of your partner and the fertilization process commences. The cells in the fertilized eggs divide and form embryos. The embryos are then implanted in the same or another woman’s uterus, with the intention of establishing a successful pregnancy. If the embryos attach to the lining of the uterus, pregnancy commences.
Basically, the procedure has 4 salient stages:
i) The patient is injected with certain drugs that aim to improve the fertility of the person by mimicking the action of sex hormones in the female. The levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) are meticulously regulated. The patient is also monitored on regular intervals via ultrasounds so that the best time for retrieving the egg is estimated. The egg is most commonly retrieved right after it is released by the follicles.
ii) Once the exact time is estimated, the eggs are given a hormonal drug called Human Chorionic Gonadotropin (HCG) so that the egg is prepared for fertilization. A hollow needle is then used to extract the egg which is then used.
iii) If the male has an abnormally low sperm count or the sperms are not as motile as they should be, instead of risking the fusion, the doctors inject the sperms directly into the egg so that there’s minimal chance of failure.
iv) The fertilized embryo is then set aside and for about five days it is subjected to incubation, until it becomes ready for implantation. It is then implanted in the uterus by the use of a catheter. If multiple embryos are available, they are frozen and stored so that they might be used in the future.
In 1978 Louise Brown was the first child successfully born after her mother received IVF treatment. Brown was born as a result of natural-cycle IVF, where no stimulation was made. The procedure took place at Dr Kershaw’s Cottage Hospital (now Dr Kershaw’s Hospice) in Royton, Oldham, England. Robert G. Edwards was then deservingly awarded the Nobel Prize in Medicine in 2010. Unfortunately, it is not surprising to see that a medicinal procedure that is about 40 years old has still not fully made its way to Pakistan. It should be alarming to see that we are so out of sync with modern medicine but sadly it has now become a well-accepted reality. While Pakistan was in the dark about it, in 2018 it was estimated that eight million children had been born worldwide using IVF and other assisted reproduction techniques.
However, IVF has its thorns as well. The most pronounced of those are mentioned below:
i) Multiple births: The foremost complication associated with IVF is the jeopardy of multiple births. This is the direct consequence of implanting multiple embryos at the time of embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (for example European countries like Britain, Belgium etc) to reduce the risk of high-order multiples (triplets or more), but these are not universally followed or accepted. Spontaneous splitting of the embryos in the womb can occur after they have been transferred, but this is rare and would lead to identical twins.
ii) Sex ratio distortions: Some forms of IVF are particularly predisposed to certain complications. Notable mentions include ICSI (first applied in 1991) and blastocyst transfer (first applied in 1984) as they have been shown to lead to distortions in the sex ratio at birth. ICSI leads to slightly more female births (51.3 per cent female) while blastocyst transfer leads to significantly more males (56.1 per cent male) being born. Standard IVF done at the second or third day leads to a relatively normal sex ratio.
iii) Spread of infectious diseases: Sperm washing is the process in which individual sperms are separated from the semen. This involves removing any mucus and non-motile sperms in the semen to improve the chances of fertilization and to extract certain disease-carrying material from the semen. Using this procedure, the risk that a chronic disease in the male providing the sperm would infect the female or offspring can be brought to negligible levels. Regarding the potential spread of HIV/AIDS, Japan’s government prohibited the use of IVF procedures for couples in which both partners are infected with HIV.
iv) Birth defects: A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a relative risk of birth defects of 1.32 (95% confidence interval 1.24–1.42) compared to naturally conceived infants. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear. However, in a population-wide cohort study of 308,974 births, (with 6163 using assisted reproductive technology and following children from birth to age five) the researchers found: “The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors.” Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Limited long-term follow-up data suggest that IVF may be associated with an increased incidence of hypertension, impaired fasting glucose, increase in total body fat composition, advancement of bone age, subclinical thyroid disorder, early adulthood clinical depression and binge drinking in the offspring. It is not known, however, whether these potential associations are caused by the IVF procedure in itself, by adverse obstetric outcomes associated with IVF, by the genetic origin of the children or by yet unknown IVF-associated causes.
Another interesting observation is that the patients who undergo IVF are placed at a greater risk for Ovarian Hyperstimulation Syndrome wherein the patient produces more than one egg, resulting in twins, triplets, quadruplets and so on. This results in swollen, painful ovaries. It occurs in about 30 per cent of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalization.
Medical complications aside, it would be preposterous to cast aside the cost factor in a poor and under-privileged country like Pakistan. Although infertility is a problem faced by the old, young, rich and poor across various cultures and races, only the hefty-pocketed can actually consider treating it. Unfortunately, despite being relatively old, it is still a relatively expensive procedure. In Pakistan, the cost of each IVF session generally falls between Rs 200,000 to Rs 400,000, depending on the hospital and doctors involved. Since the majority of Pakistanis live below the poverty line, the penetration of the idea of such a medical technique faces a formidable challenge.
IVF treatment in this country is inherently paradoxical, with any substantial discussions about it being swept under the carpet while simultaneously the hush hush market of IVF treatment is a lucrative business. The narrative around IVF or more broadly around any discussion of female reproductive health, is dominated by notions of superstition and shame. This obscures so many facts relevant to this procedure and shrouds such an important medical advancement in the same familiar cloud of ‘unethical western intervention’. The majority of our population nearly universally subscribes to the notion that infertility is a manifestation of God’s wrath, and the only avenue of treatment that they adopt is in the form of witch doctors or advice from local ‘peers’ and ‘hakeems’. This leads to many people going with all the wrong forms of ‘treatment’ in order to conceive and the results are, expectedly, horrendous. Since shame is a huge factor, many people are too timid to bring up such a sensitive issue and even if they do, they distort facts according to their convenience so that their figurative pride can be salvaged. All in all, the social stigma attached to infertility and the decades of this erroneous reinforcement have made the introduction of modern medical techniques arduous to say the least. Therefore, a tangible challenge in wholeheartedly adopting IVF treatment is to tackle layers of disinformation and fear of change that is rampant in the Pakistani society.
To properly address the issues that revolve around the general acceptance of IVF treatment is predicated predominantly on how the proverbial privileged 1% react to it. Encouragingly enough, there have been signs that the educated strata of the society are increasingly receptive to this new form of treatment. The increased awareness breeds increased acceptance and the advent of social media and the general shift towards trusting medicine, has paved the way for ideas long thought taboo, to permeate deeper into homes. This gives a very hopeful nod to the future of modern medical techniques and their application in Pakistan.
The need of the hour for our country is to have an honest and brave discussion about an issue that every individual can potentially face in their lifetime. Brushing aside such issues and hoping that they don’t rear their head around the corner does nothing but delay the inevitable. It is high time that the pioneers of healthcare grab the bull by the horns and undertake this pivotal task of warming up the ignorant and the oblivious to ideas that can turn their lives around. However, the changing landscape and socio-economic progress that the country is consistently heading towards are few exciting signs for fertility treatments. Since Pakistan is one of the few countries in the world with a very prominent youth bulge, it is imperative for us to give oxygen to discussions about infertility and endeavor to work up solutions because right now, such intervention delayed, is a child denied.