Infertility Treatments – Exploring the Latest Technologies in the Field

From 3-parent babies to using Artificial Intelligence in IVF, India has come a long way since 40 years ago, when Louise Brown brought the world’s first test-tube baby. Today, more than 8 million babies have been born as a result of IVF and other advanced fertility treatments. Estimates are that more than a half million babies are now born each year from IVF and ICSI from more than 2 million treatment cycles performed. In Europe, Spain remains the most active country in assisted reproduction.

Whilst the basics of conducting IVF have stayed the same, the technique has evolved significantly over the last four decades. Costs have come down and the process itself has streamlined. Advances in both science and technology mean that more people can achieve their dream of having a child.  

Latest advances

The field of assisted reproductive technology is rapidly progressing with many new advances in the last decade to improve oocyte quality in older women and new stimulation protocols that may improve the number of mature oocytes retrieved during an in vitro fertilisation cycle.

“Use of pre-implantation genetic screening (PGS) and finally focus on some new methods to determine endometrial receptivity are a few ways to improve fertility rates in couples,” says Dr. Archana Agarwal, Director, Mannat Fertility Clinic. 

The major issue today is that people think having excellent embryos and an excellent endometrium (lining of the uterus), should ideally enable them to get 100% pregnancy rate, but the truth is far from it. Hence, a lot of research is being targeted towards improving pregnancy rates after IVF, assisting couples who have genetic disorders to have a normal baby and to assist women who have premature menopause or primary ovarian failure to have babies with their own DNA. Some examples of the current research based on the above objectives are:

Artificial Intelligence (AI) and Machine Learning in IVF: Conventional embryo evaluation method is subjective and time consuming. Moreover, due to multiple grading systems used by different fertility centres, inconsistent selection system is also a drawback. “Newer techniques include deep learning algorithms to predict the quality of embryos; thus, ease of selection of the best single embryo for transfer,” informs Dr. Duru Shah, Director, Gynaecworld.

Molecular assessment of Endometrial Receptivity: Enables personalised embryo transfer. A microarray molecular analysis is performed on the patient’s endometrium sample and the most ideal & receptive day is chosen for embryo transfer to attain higher implantation rates.

Preimplantation Genetic Screening (PGS) testing: This is a genetic study of the embryos to select the best embryo for IVF procedure, it is also a way of decreasing the risk of miscarriage and increasing the IVF success rate. Embryoscope improves embryo selection and helps in predicting chromosomal abnormalities.

“Commonest advances that have happened over the last decade are the use of PGS, the use of blastocyst culture, assisted hatching, better developed drugs for stimulation and better methods of screening the embryos like real time images of the embryos and methods of screening for implantation failure like ERA,” shares Dr. Archana Dhawan Bajaj, Founder, Nurture IVF Clinics.

Uterus transplantation: It is a surgical procedure whereby a healthy uterus is transplanted into a woman whose uterus may be absent or diseased.

IMSI, PGD, PICSI, ERA & more: Other latest treatments for infertility include assisted laser hatching, intracytoplasmic morphologically selected sperm injection (I.M.S.I), preimplantation genetic diagnosis (PGD), PICSI (often referred as micromanipulation) technique, TESE technique, ERA and more.

ERA or endometrial receptivity analysis is a genetic test to determine the best timing for a patient’s next embryo transfer. While time-lapse embryo check allows continuous, non-invasive embryo observation without the need to remove the embryo from optimal culturing conditions. PICSI technique improves the chances of selecting the sperm for ICSI. IMSI is a technique to better assess the structure of the sperm and exclude the sperm with suspected abnormalities from being injected into the available eggs.

Importance of genetics/genomics in IVF

Procedures like IVF are becoming increasingly common and everybody’s interest is to try and find the best embryo to put back in order to get the highest possible outcome. “This is where the role of genomics and genetics comes in,” Dr. Bajaj says. Genetic screening was first applied in the context of IVF in the mid-80s, with the introduction of PGD. This technique was developed to assist couples at risk of having a child with a serious, heritable disease, following previously affected pregnancies or a family history of genetic or chromosomal disorders. The process involves IVF embryos being analysed genetically, with only unaffected embryos selected for implantation.

Before PGD, couples deemed to be at risk had to wait for invasive testing during established pregnancies, risking an increased chance of miscarriage. Furthermore, genomics is routinely involved to optimise results in most progressive nations worldwide where IVF, ICSI, and regular blastocyst hatching have now become a routine.

“Genetic tests play a significant role to provide direction toward the most appropriate assisted reproductive techniques,” says Dr. Anubha Singh, Medical Director, Shantah IVF Centre. A detailed family history for a couple planning to undergo ART is a useful tool for identifying genetically at-risk couples and can improve the medical care of these patients.

A number of important factors must be considered when collecting a detailed family history in the context of family planning such as the history of the patient’s pregnancy (for example, multiple abortions may indicate a chromosomal abnormality), the degree of kinship given (particular attention should be given to first- and second-degree relatives who may have a history of mental retardation, learning difficulties, progressive muscle weakness, early cataracts, infertility, motionless birth, recurrent miscarriages, and coagulation disorders). Also, the consanguinity of the couple and the ethnicity of both groups of grandparents.

Tests are also indicated for the identification of genetic diseases that are transmissible to the offspring: preconception screening allows couples who are planning to become pregnant, to know their reproductive risk. Normally, gametes with genetic or chromosomal alterations have reduced reproductive potential. Thanks to ART, many of these difficulties can be overcome, and therefore, genetic tests have the crucial impact of monitoring the possible transmission of these genetic alterations to the offspring. “Thus, genetic tests are becoming increasingly relevant in reproductive medicine,” says Dr. Shobha Gupta, Medical Director and IVF Expert from Mother’s Lap IVF Centre.

Some of the uses of genetics/genomics in IVF include:

• Preimplantation Genetic Analysis and Diagnosis help choose embryos with highest chance of implantation and reduce the risk of passing on any genetic abnormalities to the offspring.
• 3 Parent Babies is a modified version of IVF, wherein the healthy mitochondria of a donor woman is mixed with the DNA of 2 parents. “This involves isolating mitochondria from oocyte precursor cells of the patient’s ovary and injecting it into the patient’s own oocytes during fertilisation,” says Dr. Shah. This improves embryo development and gives better results in live birth rate (LBR), though randomised trials are yet to be established.
• Chromosome micro array and Next Generation Sequencing (NGS) have been developed to screen every chromosome comprehensively in a single sequencing run. It picks up any genetic mutations or chromosomal aberrations and is highly sensitive.

Researchers have grown the human embryo in the lab successfully till day 13 of life. This feat is a huge milestone in the advent of IVF.

Challenges & possible solutions

According to the Indian Society for Assisted Reproduction (ISAR), India is set to become the international hub for IVF and surrogacy. The IVF market in India is estimated to cross the Rs. 20,000 crore mark by 2022. IVF treatments in India have been on the growth since the 90s, when people used terms like test tube baby. Though today, the internet and the Indian media has played a major role in bringing awareness about IVF and surrogacy. Earlier, infertility was a taboo and people looked down to infertile women; but today, treatments available for infertility are a common practice in the society. “There is no iota of doubt that fertility or IVF clinics in India are mushrooming day by day; it is important though to properly follow the guidelines set by ICMR,” cautions Dr. Gupta.

Challenges faced in this sector are at all levels including the procedure itself; it begins with a diagnosis, social infrastructure, challenges related to cost, failure, and repeated attempts.  “IVF increases the risk of multiple births if more than one embryo is transferred to your uterus,” Dr. Agarwal says. A pregnancy with multiple foetuses carries a higher risk of early labour and low birth weight than pregnancy with a single foetus does.

Then there is the challenge of optimising results and that is where all the recent advances come in. The world is trying to move beyond embryo biopsy and finding ways to grow embryos, by way of getting cell free DNA and studying the genomics of the embryo from that. This process can do away with the risk of causing any harm to the ongoing child.

“There are so many issues and grey zones in the infertility treatment, which in itself is a huge challenge,” says Dr. Bajaj.

Moreover, the system needs to be much more regularised in India as many ill-equipped players have started running IVF facilities in this sector. Having a less experienced staff is a major hurdle as well. In addition, strict guidelines should be followed to refrain from exploitation in the medical field as IVF and surrogacy has seen a major increase in recent years, but experts warn that couples should know where and when to see an IVF specialist.

“There are very few centres that are doing good ethical work,” says Dr. Shweta Goswami, Medical Director Zeeva Fertility Clinic and Sr. Consultant-IVF at Cloud Nine Hospital and Jaypee Hospital, Noida.

These kinds of challenges can be overcome only by creating patient awareness.

“Cost of ART is a major challenge as all culture media, catheters, etc. are imported with heavy duty on them. Here, some Made in India initiatives would definitely bring down costs,” says Dr. Shah.

In addition, medical treatments should be provided in government hospitals for the people below poverty line. Government should introduce such a system in which people living in below poverty line should also be eligible to take IVF treatments in private hospitals. Expensive medicines should be made available at cheaper rates for those people across all the medical stores in the city.

There is also a sustainable growth in the country’s GDP due to medical tourism, when patients come to India to take an IVF treatment. Hence, there must be a provision to avail visa benefits not only for them but for their family members as well.

Age is also one of the biggest challenges in IVF. Timing is very important. There are a number of factors, which come into play. From lifestyle choices to the reasons for infertility, everything matters. “A key role is played by the age of the woman who will carry the baby. Women in their 20s and 30s experience the most successful IVF implantation,” Dr. Goswami avers.

This is because of the viability of the eggs, which facilitates in natural fertilisation. The morbidity of the foetus increases with the age of the mother, and thus, the patient must be made aware of all the risks involved with old age pregnancy. In fact, many patients start trying to conceive at the age of 38-39. Thus, it is vital to educate people that age has a big impact on their egg quality and IVF results also, so we should do it in a very timely manner.

Additionally, there is social stigma around IVF, though there is much openness about IVF in today’s time, but people still either don’t want to disclose that they went through IVF or worse, do not want to take the IVF route at all. “Currently, only 1% of infertile couples seek any kind of fertility treatment,” Dr. Singh Says. That means awareness is still lacking, she adds.

Medical insurance of IVF is also a major setback in India, as very few insurance companies cover this treatment. Also, less government funding is a major hindrance as there are not many classy government institutes in India, where cost is not a constraint.

Road ahead

To overcome the challenges in the field of ART, we need to retrain ourselves, which means the patient, society and even the doctors. More involvement from the government agencies and the private players as well would go a long way in bringing about the much-needed change in infertility treatment perspective in our country.

Some organisations have cut down costs for the armed forces, including all military and para military forces. Similarly, other organisations can pick up any one sub section of the society and try to help them in their journey. Additionally, the government needs to look at the fact that Ayushman Bharat means a healthy and happy India and having children is a major contributory factor to health and happiness.