World IVF Day – a day for hope and positivity

World IVF Day is a day to celebrate science and be hopeful.

On this World IVF Day, my message to everyone, especially to those undergoing treatment for infertility, is to stay hopeful. Scientific advancements have significantly simplified the process and improved the treatment outcome, since the first successful IVF procedure back in 1978, which resulted in the birth of Louise Brown in the UK.

If you are struggling to conceive, my suggestion is to consult an infertility specialist now and start treatment early.

When to consider ICSI?

ICSI is a specially useful embryological technique for treatment of male infertility and repeated IVF failure. ICSI is now very much a standard procedure being sued in well over half of all treatment cycles in India.

What is ICSI?

ICSI is now a well-established microinjection technique which has helped thousands of infertile men to overcome issues with sperm parameters. It is also useful in cases of fertilisation failures with repeated IVF cycles. The technique evolved in 1990’s in Belgium and since then has become established as one of the biggest discoveries in the management of infertility. Presently more than 50% IVF cycles in India and up to 63% IVF cycles in USA are ICSI cycles.

How is ICSI different IVF?

ICSI is mainly an embryological process. The process of ovarian stimulation, egg retrieval and embryo transfer remains the same as in IVF (described above). The male partner provides a semen sample on the same day by masturbation. Alternatively, sperms retrieved surgically from testis (in case of obstructive / un-obstructive azoospermia) or sperm that has been previously cryopreserved can also be used. So, technically the number of sperms required is only as many as the number of eggs that can be fertilised.

The eggs are also processed differently for ICSI, as they are first cleaned in order to clean them and remove the debris and outer cumulus cells. The eggs are screened for maturity under a microscope and the mature ones are selected for micro-manipulation or ICSI. One carefully selected sperm is injected into each selected egg using a micro-manipulator under high magnification microscope. Later the fertilised eggs are placed in the incubator and allowed to grow.

Who benefits from ICSI? Who are potential candidates for ICSI?
  • ICSI benefits all mainly men with low sperm count , poor motility or morphology
  • In cases with surgically retrieved sperms like MESA, TESA, TESE, where this is the only tool to fertilise the egg.
  • In pts with recurrent fertilisation failure with IVF.
  • In patients undergoing preimplantation genetic diagnosis.
What are various risks associated with ICSI?

ICSI revolutionised the treatment of male factor infertility enabling even males with nil sperm count to father their own genetic child. It is a fairly safe procedure. But, some studies have indicated a marginal increase in risk of congenital malformations in the offspring (six per thousand births compared to two per thousand births in general population). But it still remains to be proven if the real cause of the higher incidence of congenital malformations in such children is ICSI or just a transmission of genetic abnormalities from the male with severe sperm abnormalities.

Contact Dr Parul Katiyar for more information about ICSI and the treatment of infertility.

Tags: Male Infertility Treatment in Golf Course Road Gurgaon, Infertility Treatment in Golf Course Road Gurgaon, Male Infertility, What is ICSI, Infertility Treatment in Sushant Lok Gurgaon, IVF Treatment in Sushant Lok Gurgaon.

Saviour Siblings – Is it a boon or a bane?

Artificial Reproductive Technology (ART) has been a boon for infertile couples, who have been able to overcome their childlessness through various advanced ART techniques. Besides helping infertile couples, ART combined with preimplantation genetic testing also helps in identifying and eliminating the risk of transmission of several genetic diseases from the affected or carrier parents to their offspring. Another important and evolving therapeutic application of IVF combined with preimplantation genetic diagnosis (PGD) technique is to  identify create “saviour embryos”, which will help in giving birth to babies commonly known as “saviour siblings”.

Saviour Sibling

The possibility of “saviour sibling” has existed at a global level for last three decades, but it came under limelight in India very recently with the birth of one of the first Indian saviour siblings in Ahmedabad, with the procedure performed at Nova IVI Fertility centre. (Read this news here –

So, what is a saviour baby or a saviour siblings? A saviour baby or asaviour sibling is “a child who is born to provide life-saving tissue to an existing childaffected with a fatal disease that can be best treated by tissue transplantation”. This has become possible by using IVF technique in conjunction with PGD to identify the embryo for implantation, which is HLA matched with the affected sibling. Therefore, the doctors are able to select an embryo for transfer which, if successfully implanted, will become a “saviour sibling” – a sibling capable of donating life-saving tissue to the affected child.

Patients with diseases like certain leukemias and anemias need bone marrow transplant (BMT) as part of their treatment. However, BMT requires a donor who is an immunological match to the receiving patient. In most of the cases, a biological sibling of the patient is the best possible donor, as the siblings would share the same gene pool. Typically, there are 4 possible combinations resulting from mix-and-match of genes coming from the two biological parents. Thus the siblings have a 1 in 4 chance of a HLA (human leucocyte antigen) match.

Though the practise of saviour siblings can be life saving for the affected children who would otherwise have died in absence of appropriate treatment, the practice is also debatable with several critics raising ethical concerns on the procedure ever since it first got reported.

The key concerns raised by the critics around the concept saviour siblings include :

  1. Intention of the parents – critics argue that only intention in the creation of saviour siblings is to save the life of an existing child thus it involves ‘instrumentelizing’ the child that is created by bringing it into existence as a means to the end of saving another child’s life. However one can also argue that ultimately the parents of the saviour siblings will love the child for its own sake.
  2. Psychological impact on the saviour sibling once she/he grows up – Any child born as a result of the need for a saviour sibling will grow up with the realization that they were conceived for the sake of making tissue for transplant; the circumstances of their conception may have psychological consequences. This will not be a concern if instead of creating saviour babies, we only consider creating “saviour embryos” where, if instrumentalization occurs, it occurs without any consequences for any particular person. Therefore in a certain way, creation of saviour embryos is arguably more ethical than the creation of saviour siblings.
  3. Creation of designer babies – Critics argue that this concept may be misused by willing parents to create designer babies, and this could mean a gross misuse of this technique. This concern can only be addressed by carefully drafted and strictly followed regulations.

It is, therefore, very important to recognize that while this is a potentially lifesaving technique, it is also carries significant potential of misuse for selfish gains and for significant psychological impact on these babies. Thus, it is imperative that this procedure is regulated with strong regulations in order to prevent it’s abuse for non-clinical purposes and to protect the rights of the saviour siblings. This will help in striking the bright balance between the need to save a life and to save the rights of the saviour.

Please contact me at, if you need to know more about saviours siblings and in what disease conditions they could be considered.

How should an international patient select an IVF services provider in India


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Ever since the second IVF child in the world was borne in Mumbai in year 1978, India has made rapid strides in the field of infertility care. Over these 40 years the no of registered ART service providers in India has grown to over 400 (as per ICMR Registry of ART centres). Several of these centres are equipped with the latest technological infrastructure, have highly experienced clinicians and deliver success rates at par with the best centre across the world. These facts also make India one of the most favoured destinations for international patients seeking infertility treatment.

However, the international patients coming to India for treatment need to be careful while selecting the fertility clinic and treating experts. As per estimates, there are over 2,000 active ART service providers in India and most of the renters located in cities with international air connectivity try to attract patients from abroad. The patients, therefore need to exercise some caution and do their homework well before making their choices. Here is a quick guide cum checklist which can help patients make educated choices for their infertility treatment in India.

  1. Ethical treatment
    1. Make sure to read, understand and sign an informed consent before starting treatment
    2. Ask for “Real time”, comprehensive & non – editable data capture, and for complete, comprehendible and timely information sharing
    3. Ensure the centre and the treating clinicians are following the law of the land with respect to treatment options like surrogacy
  2. Transparent pricing
    1. Know what is included and what is excluded in the packages
    2. Beware of “Buy one, get one free” schemes – you need the best care, nit a guarantee against failure!
    3. Understand the surrogacy and donor programs the centre is offering, as these typically come with surprises
  3. Credibility of the centre and treating doctors
    1. Ask for the academic credentials and experience of the treating doctors
    2. Check if the centre has clinical protocols based on scientific evidence in place
    3. Check for the experience of embryology team
  4. Clinical excellence
    1. Check the treatment success rate for both centre and the treating doctor
    2. Ask if there is some published data and literature for documented success
    3. Do look out for genuine patient testimonials
  5. Infrastructure and accreditation
    1. Ensure the centre has good laboratory infrastructure and has advanced treatment facilities
    2. Check if the centre has all valid licenses to offer treatment and has been accredited by the agencies like NABH/ ISAR/ FEQH
    3. Make sure the centre is easily accessible and the locality has a community to support international guests like you
  6. Patient centric treatment approach
    1. In-house counselling in a comforting environment
    2. Ensuring care and compassion during treatment
    3. Comprehensive services at every centre

I hope this information helps patients make better decisions. Please contact Dr Parul Katiyar at, if you have any questions regarding infertility treatment in India.

Five questions to ask while choosing an Infertility Clinic

We are living in an age of consumerism, and healthcare has also been affected by it. In India, several Infertility clinics and IVF centers have come up over last few years. While this has helped fill in the demand supply gap in this field bringing in much needed competition and has given more options to the patients, this has also prompted aggressive marketing by these clinics is in order to attract more patients, thereby confusing patients on how to go about choosing their doctor and treatment center. Healthcare is a very sensitive subject and we have to be able to filter the right information from all the noise in order to be able to make the best decisions for ourselves.

In my own clinical experience, I have had several couples who have consulted me for their inability to have a child, and who were confused due to information overload on the subject and vastly varying offers and claims from infertility clinics. Patients often ask me how should a patient decide which infertility clinic is best for them and what parameters should they consider when selecting an Infertility clinic for treatment. I suggest my patients to ask these five questions before selecting an infertility specialist doctor and an IVF clinic for treatment.

Question 1 – What is the real cost of IVF treatment at the center?

Nowadays there is a flurry of ads on radio, newspapers and digital platforms, several of which try to attract patients by advertising the lower cost of IVF – at times claiming to do an IVF cycle for as low as Rs 25,000 only, while at others offering one IVF cycle free with one paid cycle. The lower cost of treatment is always better for the patients. However, it is important that patients also understand the “conditions apply” clause and read in between the lines to understand the overall cost implication before making their choice on the basis of low cost alone, so that they are not taken for a ride!

It’s important to understand that a typical IVF cycle includes several steps, namely  investigations of the couple, hormone injections for 10-11 days in order to stimulate maturation of eggs, the procedure of egg retrieval and finally transfer of embryo into the lady’s uterus. Patients should understand and take into consideration the overall cost of treatment, as at times the advertised cost may not include cost of hormones and investigations which contribute significantly to the overall cost of a cycle.

Question 2 – What is the success rate of IVF at the clinic?

Another very important parameter to check is the success rate of the clinic and also understand how the claimed success rate was calculated. While the success rate for IVF do vary from one center to another, and the patients should certainly go for treatment at centers with superior pregnancy rate, it’s important to do an apple to apple comparison of success rates.

The pregnancy rates are generally much higher in younger women undergoing IVF. Similarly, success rate for IVF is much higher among infertile couples using donor eggs as compared to the ones using their own gametes. Therefore, the claimed success rates at clinics doing a lot of donor egg cycles can actually be higher than centers with a more balanced distribution of cases.

My simple advice on this point is – if a clinic offers donor egg option without any justification or declares the patient to be having poor quality of eggs based on an ultrasound report and without doing an IVF cycle, the patient should get alert and seek a second opinion before making a decision. As such there is no way to assess the egg quality based on ultrasound or blood reports, which, at best, can estimate the ovarian reserve. There is no way to evaluate the egg quality other than to take the eggs out and check them for quality in the lab.

Question 3 – What is the incidence of multiple pregnancies with IVF at the center?

The aim of any infertility treatment is to enable a couple have a healthy child. So, one should always ask what is the protocol for the maximum number of embryos transferred in a cycle at the clinic.

There is a tendency to transfer more than one embryos in a cycle, which is based on the assumption that the chances of pregnancy in a cycle increases by transferring multiple embryos. However, the best outcome of a cycle can be achieved by transferring 1 or maximum 2 properly selected embryos. Not only does multiple embryo transfer not increase the chances of pregnancy, it, in fact, increases the risk of multiple pregnancies, thereby increasing the risk to both mother and child. Multiple pregnancy is the biggest complication of IVF treatment and the risk of multiple pregnancy is directly proportional to the number of embryos transferred in a cycle.

Question 4 – How good is the IVF lab at the center?

This is an often ignored aspect while choosing an IVF center over the other. But, a well-equipped and maintained lab is a crucial factor differentiating a good IVF center from a not-so-good center. Patients should understand that a well-equipped lab with strong quality control and quality assurance program will always do more justice to their eggs, sperms and embryos and maximize their chances of pregnancy. A good IVF clinic needs to have a good embryo freezing program in order to properly manage the extra high quality embryos from an IVF cycle for possible use for the same patient in future. This helps in preserving the precious embryos and also reduces the cost of possible IVF interventions in future. Many centers claiming a low cost IVF often don’t have a good embryo freezing options for the patients.

Likewise, a properly trained and experienced embryologist also plays an important role in success of the IVF program. So, patients should inquire about the background and competence of the embryologist also while they do the background check on the treating clinician.

Question  5 – Does the center have patient support program?

This is another lesser investigated aspect while choosing an infertility clinic for one’s treatment.  In my view, availability of a good support team including fertility counselors is as important a factor as having a good infertility specialist doctor in improving the success of IVF treatment. Good counselors help the patients understand their issues holistically and helps them overcome the stress associated with infertility. This, combined with the skills and personalized attention of the treating doctor, plays an important role in improving the outcome of IVF treatment.

So, next time you see an enticing, “too good to be true” offer for IVF treatment at an infertility clinic, stop and ask yourself these five questions before falling for it. Always remember, choosing the right infertility expert and the right infertility clinic for your treatment will largely decide the outcome of your treatment!

Do write to me at if you have any questions about IVF.

Three strategies to minimize multiple pregnancies with IVF treatment

Having twin pregnancy has become almost synonymous with undergoing the IVF treatment. And, my patients often ask me if they can conceive only twins with IVF? Here I share what are the best practices to optimize the outcome of IVF treatment and minimize the incidence of twin pregnancies.

With rising incidence of infertility, IVF treatment becoming more commonly available and all the technological innovations with IVF procedure, there is an ever growing focus on minimizing the complications associated with IVF treatment. One of the common risks associated with IVF, which is also a major cause of distress among couples preparing to start IVF treatment, is the risk of multiple pregnancies. In fact, having twin pregnancy has become almost synonymous with undergoing the IVF treatment. And, my patients often ask me if they can conceive only twins with IVF? In reality about 1 in every 4-5 pregnancies resulting from ART are twins, a rate much greater than in the general population (1 in 80 pregnancies). The incidence of triplets and quadruplets is also higher among women undergoing ART. However, the majority of ART pregnancies (about 70%) are singletons.

The risk of multiple pregnancy in IVF cycle exists primarily because of the tendency to transfer more than one embryo inside the uterus to increase the chances of pregnancy. This is done as there are no tests or procedures which can assure us of pregnancy after IVF. The process of implantation of an embryo in the womb is a complicated one, and what  transpires between the embryo and the womb that results in positive or negative pregnancy outcome is not fully understood. Therefore, in order to increase the chances of transferring an appropriate embryo, more embryos are transferred at a time. But, this puts the woman at risk of multiple pregnancy. But this does not mean that in the pregnancy rates increase proportionately to the number of embryos transferred. In fact, rather that increasing the overall pregnancy rates, transferring more than one embryos in one cycle actually increases the risk of multiple pregnancies, as more than one embryo may implant at a time.

Having twins may actually even sound tempting to many patients who have struggled to have a baby for long, but it is not as good as it sounds. Multiple pregnancy is associated with a higher rate of maternal, fetal and neonatal complications and is now considered as the single biggest risk of fertility treatment. Good practice in IVF aims to reduce risk of multiples in an IVF, whilst maintaining the overall chances of becoming pregnant. This is achieved by proper patient selection and counselling. I follow these three simple strategies to achieve the best clinical outcome from IVF procedure –

  1. Young women who have the best chance of conception also have the highest chance of conceiving multiples, so I prefer to do single embryo transfer in these patients. The remaining embryos can be frozen and preserved for later use
  2. An extended culture of embryos up to the day 5, called as blastocyst culture, allows us to select the best embryo for transfer, thereby improving the chance of pregnancy with single embryo transfer.
  3. For carefully selected set of women, who have had multiple IVF failures and who are not fit or willing for blastocyst culture, I transfer two high quality embryos, which gives the best possible chance of pregnancy with minimum possible risk of multiple pregnancies.

To sum it up, we need to counsel all our patients that only success parameter in any IVF cycle is a healthy baby born to a healthy mother, and reducing the number of embryos transferred in a cycle is a significant step in achieving this objective. Patients should be counselled about the risks associated with transferring many embryos and also explained the option to freeze the spare embryos, if any. If needed, subsequent cycles with both fresh and frozen embryos would give them even better cumulative pregnancy outcome than putting in several embryos in one cycle itself.

Do write to me at if you have any questions about IVF.


Management options for Endometrioma associated with Infertility

Endometriosis is a problem often associated with infertility. In my clinical practice I have seen many women with endometriosis who have to undergo a battery of investigations and try several treatment options to overcome the pain, dysmenorrhoea and infertility associated with endometriosis.  A significant number of these women also present with cyst in their ovary which are called as endometrioma.

Endometriomas have most commonly been treated surgically. But, while surgical treatment for endometrioma is very common, surgical treatment has no clearly documented role in improving fertility of women undergoing surgical intervention for endometriotic cyst. Surgical treatment for endometrioma in infertile patients should be reserved only for a small section of young women, as it improves spontaneous pregnancy rate among young women. However, surgical treatment has no definitive advantage over expectant management in majority of women with endometrioma and it may actually reduce a woman’s ovarian reserve .Some of the other indications of surgical intervention in infertile women with endometrioma include cysts blocking access to ovary for egg retrieval during IVF, to treat concomitant pain symptoms or in cases where malignancy cant otherwise be ruled out with reasonable accuracy.

Women with endometrioma generally have lower ovarian reserve than their age matched control group. Therefore, I recommend proceeding directly to IVF in order to reduce time to pregnancy. Despite of a negative impact on ovarian reserve and ovarian responsiveness, the results of IVF treatment in women with infertility associated with endometrioma are comparable to overall results of IVF in women with tubal factor infertility.

This also holds true for all women with endometriosis associated infertility, especially when the disease is of significant severity. I recommend aggressive treatment of infertility in these women for the best outcomes, because the chances of spontaneous pregnancy in these women are rather low.

Please write to me at if you have any questions on endometrioma and associated infertility.




IVF – A blessing or a bane?

Many patients who have been advised IVF treatment wonder if they will have a normal baby at the end of it and if the IVF carries higher risk of certain disorders. Education from credible and scientific sources helps bust several myths on this subject.

As an IVF specialist I often come across questions from my patients about safety of IVF procedure and the well being of the offspring resulting from IVF. Many patients ask me if the IVF baby could, in any way, be different from a normally conceived baby, and are, at times, reluctant to undergo the fertility treatment. Many of these patients quote some horror stories of other patients who have undergone IVF.

What I explain to the patients is that most of the times they get to hear just one side of the story. I try to make them understand that IVF is a medical procedure used to help couples conceive who find it difficult to conceive for several biological reasons. Just like all other medical interventions, IVF also has its own set of disadvantages, and can, at times, cause inconvenience to women undergoing treatment.

If you have been recommended to undergo IVF as the best way to conceive, I suggest you  not to form any preconceived opinions about the procedure based just on hearsay. Instead, you should discuss the pros and cons of the procedure, possibility of its success and chances of any inconvenience etc with your treating specialist and to educate yourself about the science behind the procedure from authentic sources. As Benjamin Franklin once said – “An investment in knowledge pays the best interest”!

I will continue to write on this subject to answer some frequently asked questions and address the common myths about fertility treatment, specially using IVF. Do write to me at if you have any questions about IVF.

Looking beyond Semen Analysis as a marker for Male Fertility

Its often difficult to pin down the real cause of male infertility as the assessment of the male partner remains restricted to semen analysis and a normal report is used to rule male factors out. Many of these incompletely evaluated men and couples can benefit from further investigation of the male partner, which not only helps start proper intervention for conception early on, but also saves lot of mental stress and stigma for the woman partner.

It’s a well-known fact that male factor contributes to a couple’s inability to conceive in up to 40% of all cases of infertility. In practice, however, the inability of a couple to conceive is still seen largely as a woman’s problem. In fact, one of the most common initial responses of the male partners that we come across when assessing them is that all “I am healthy and all my reports are good” and then the whole responsibility is shifted to the woman partner alone.

So, what does “my reports are all good” actually mean? This refers to normal semen parameters as noted on standard semen analysis. But then the real question is if a normal semen analysis report indeed rules out male factor infertility! Recently there has been a big debate on how good a good semen analysis report actually is and if it is an accurate indicator or predictor of a man’s fertility. Well, the simple answer is No, it is not!  And, even though semen analysis offers a good initial assessment of male partner, there is more to sperm health and function than what a standard semen analysis picks up. It is now 300 years since Leeuwenhook first identified sperms under the microscope, yet it seems that we have only just begun to intelligently evaluate the concept of male Infertility and till date semen analysis remains the cornerstone for evaluation of male fertility.

Sperm production in the testis is a lengthy and tedious process and any adverse influence during the sperm production or maturation process can lead to an adverse sperm health and/or quality. According to estimates, up to 10% of men having normal semen parameters can actually fail to conceive due to undetectable damage in the spermatozoa. These men can be infertile without actually being aware of it and are often classified as unexplained Infertility, unless they are further investigated properly. Therefore, it is very important that the evaluation of male partner is not limited to only semen analysis, and is combined with comprehensive history taking, clinical examination and relevant endocrine /genetic investigations.

The real shortcomings of semen analysis include its inability to predict the fertilization potential of the sperms and the overall functional health (DNA integrity) of the sperms. Thus there is an increasing awareness about the need of supplementary tests to evaluate male partner and look beyond only semen analysis to assess the male factor infertility.

The reasons for infertility in such men can be attributed to development of anti-sperm antibodies, which interfere with a sperm’s ability to fertilize the egg. These antibodies cannot be detected on routine semen analysis and we need specialized tests to detect them. Also, the tests to detect anti-sperm antibodies have been in existence for a long time but since there is no particular treatment for this condition, these tests have not gained a lot of acceptance in clinical evaluation of infertile men. However, since these men benefit from IVF or ICSI for conception, an early detection of anti-sperm antibodies helps in overall management of the couple.

Another very common, and often missed, cause of male factor infertility is damaged sperm DNA. As discussed in one of my earlier articles, DNA is the basic genetic material and any abnormality or alteration in the sperm DNA affects its fertility potential – not just for natural conception, but also for IUI and IVF treatment. Damage to sperm DNA can happen at any stage of its development, maturation or transport – starting from beginning of spermatogenesis till the time of ejaculation. A number of factors can cause high DNA fragmentation. These include lifestyle factors such as smoking, excessive drinking and drug abuse, advanced age, exposure to environmental toxins, varicocele and infections causing oxidative damage to DNA.

One more factor leading to male factor infertility is dysfunctional sperms, as a result of which the sperms  may not be able to fertilize the eggs naturally. All these causes of infertility may be present in men with normal semen parameters.

ICSI has helped numerous couples with male factor infertility with seemingly normal semen parameters conceive by injecting the sperm directly into the egg for fertilization. This technique helps bypass many of the shortcomings of the sperms, but also increases the risk of selecting defected sperms, which could then pass  onto the offspring.

There is a lot of research in the field of andrology to understand and improve the health of sperms. This can help in not just improving the diagnosis of infertility and reducing the burden of unexplained Infertility, but also devising directed therapies to improve outcome of fertility treatments.

I will write about what should be done for couples having unexplained infertility with the male partner having normal semen parameters on semen analysis.

For any questions, please write to me at

Five frequently asked questions about genetics of Recurrent Pregnancy Loss

Miscarriage is a very traumatic experience for any woman or couple and can often mean loss of hope for couples finding it difficult to conceive. Recurrent miscarriages, also known as Recurrent Pregnancy Loss (RPL) is naturally even more distressing and worrisome for the affected couples. While a lot about the causes and reasons for RPL still remains mystery, we know that genetic factors play a significant role in causation of RPL. This aspect of RPL is not generally well understood by the affected couples owing to the complex science behind the same. This article is an effort to explain the genetics of RPL in simple language to bridge the gap in knowledge for the common people on this subject.

Over last ten years, I have consulted and counselled hundreds of couple who have suffered pregnancy loss, either in form of miscarriages or stillbirths. Miscarriage (also known as pregnancy loss) is a relatively common problem encountered in up to 15 to 25 % of all clinically recognized pregnancies, and in many of these cases the actual cause of pregnancy loss remains unidentified.

Most of the miscarriages are sporadic in nature and can be attributed to defects within the fetus. However, some woman may lose their pregnancy repeatedly. Recurrent pregnancy loss (RPL) is defined as loss of three or more consecutive clinically recognized pregnancies and affects around 1% of couples actively trying to conceive. RPL causes significant anxiety for the suffering patients, especially for the pregnancies resulting from fertility treatment. In addition, RPL in patients undergoing fertility treatment also causes significant financial stress for the couple.

Both Maternal age and number of previous miscarriages independently increase the risk of miscarriage in the subsequent pregnancy. However patients with RPL still have a remarkably good prognosis for live births. Also, the overall incidence of pregnancy loss with IVF pregnancy is almost same as in wider population.

The real cause of RPL remains unknown in up to 50% of the women, despite of all the advancements in diagnostics. The known causes of RPL include –

  1. Genetic Causes
  2. Immune Causes
  3. Anatomical Causes
  4. Hormonal Causes
  5. Environmental and occupational causes

While genetic abnormalities in the fetus are known to cause up to 50% of sporadic early pregnancy losses, only about 2 to 5% cases of RPL can actually be attributed to genetic abnormalities in the fetus. In this article, I will focus only on  understanding of genetics of reproduction and genetic causes of RPL. I will discuss other causes and management of RPL in my upcoming posts.

Here are five things you need to know about the genetic causes of RPL

  1. What is a chromosome?

The basic genetic unit of human body is “DNA”, which is packed together to form “Gene”. Genes are the working sub-units of DNA and carry the information that determines the features or characteristics passed on from one generation to another. Human beings are estimated to have between 20,000 to 25,000 genes. Genes are located inside the nucleus of cells and are found on thread like structures, known as which are the “Chromosomes”.

Chromosomes are arranged in pairs inside nucleus of the cells. Each human cell normally contains 23 pairs of chromosomes, with one chromosome of each pair inherited from one of the parents. The first twenty two pairs of chromosomes are same in both men and women, and are known as “Autosomes”. The 23rd pair is known as the “Sex chromosomes” and is   identified as either “X” or “Y” chromosome. The type of sex chromosome determines the gender of the person, with females having two X chromosomes and males having one X and one Y chromosome.

Every person has got 2 copies of each gene, one inherited from each parent. While most of the genes are same in all individuals, a small number of genes (< 1%) are unique for each individual and these genes eventually make all human beings individual.

  1. What is cell division?

In order to grow and reproduce the cells have to continuously divide to produce “daughter cells”. This cell division can be of two types- mitosis or meiosis. Without getting into technicalities, it would suffice here to know that the sex cells (both male and female) divide by meiosis and one cell produces four cells (known as gametes – eggs in women and sperms in men) at the end of the division.

  1. How is the fetus formed?

An embryo is formed when the egg and sperm meet each other and the sperm penetrates the wall of the egg, thus bringing its own genetic material into the genetic material of the egg. This process, known as fertilization of the egg, produces a cell with full set of genetic material (23 pairs of chromosomes) for the offspring. The embryo thus formed multiplies repeatedly and very quickly to create a mass of cells, which then differentiate to form different organs of the future baby.

  1. What are common genetic anomalies which can cause RPL?

A variety of genetic factors can cause pregnancy loss. The commonly known causes include-

  1. Aneuploidy- an extra number of chromosome
  2. Translocation and inversion of chromosomes- fault in structure of chromosome
  3. Deletion or duplication of chromosome- fault in amount of DNA in a chromosomes
  4. Single gene mutations- chromosomal abnormality at the level of genes

Aneuploidy – Aneuploidy is an error of cell division, which results in the “daughter” cells having wrong number of chromosomes. In some cases there is a missing chromosome, while in other cases, there is an extra chromosome inside the cell. Thus, such individuals with aneuploidy may have cell with 45, 47, or 48 chromosomes. Such individuals will have cells with improper genetic information, which can result in miscarriages. In some cases with aneuploidy (as in cases of Down’s syndrome), the fetus may survive but the child is likely to be born with various abnormalities. The most common aneuploidies are extra chromosome number 16, 18, 21.

Translocation – In translocation, a segment from one chromosome is transferred to another chromosome or to a new site on the same chromosome. Translocation could either be non-reciprocal, in which there is a one way migration of chromosomal segment or reciprocal, which involve exchange of segments from two different chromosomes. Translocation leads to alteration in the alignment of the genetic structure of the fetus and could, in some cases, result in miscarriage.

Inversion – An inversion is a chromosomal rearrangement in which the affected segment of a chromosome is reversed end to end, and typically occurs when a single chromosome undergoes breakage and rearrangement within itself.

Inversions and translocations may not cause any genetic abnormalities in carriers (parents), as long as the rearrangement is balanced with no extra or missing DNA. However, the gametes (eggs and sperms) in affected people carry unbalanced (excess or insufficient) amount of genetic material. The resultant pregnancy is, therefore, genetically abnormal and can lead to infertility, recurrent miscarriages and sometimes increased risk of cancer.

Deletion and Duplication of Chromosomes – In deletion, a portion of the chromosome is missing or deleted, whereas in duplication, a portion of the chromosome is duplicated, resulting in extra genetic material. Both these genetic abnormalities can lead to various kinds of syndromes in the offspring.

Single gene mutation – Single gene mutations are caused  by DNA alterations within one particular gene. These mutations can affect the mother or the fetus.

Mutations in the mother can interfere with implantation of the fetus, thus causing infertility or recurrent miscarriage. Some examples of maternal single gene disorders include maternal myotonic dystrophy, connective tissue disorders like Marfan Syndrome and Ehler Danlos Syndrome and sickle cell disease.

Single gene mutations in fetus, which could lead to RPL include autosomal dominant lethal skeletal dysplasia, Type 2 osteogenesis imperfecta, autosomal recessive disorders like Alpha Thalassemia and X chromosome linked disorders which typically are lethal in male fetus.

  1. What are chance of live birth after RPL

The chances of having a live birth after recurrent miscarriages are not as grim as they appear. The overall probability of live birth after RPL for women aged between 30 and 34 years of age is approximately 66- 70%. The probability, however, goes down with each extra pregnancy loss beyond 3 and increasing maternal age. Newer technologies like “Preimplantation Genetic Diagnosis” (PGD) can help in improving the chances of live birth in couples with known genetic disorders, as it helps in selecting the embryos with the correct genetic composition before transferring into the uterus.

Thorough evaluation of couples who have already encountered miscarriages in two consecutive pregnancies is recommended, because the risk of another miscarriage after 2 lost pregnancies is already almost 30% compared with a risk of miscarriage of 33% after 3 lost pregnancies.

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