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.

Please write to me at if you have any questions related to RPL or if you need more information on this subject.

Seven frequently asked questions on “Poor Ovarian Reserve”

Poor ovarian reserve is a major cause of reduced fertility among women who delay planning a family. Many of these women remain unaware of this reality and dont know that there was means to preserve their eggs for a delayed child bearing.

Ovarian Reserve is one of the more frequently discussed topic in my infertility practice, especially as many working women plan to defer child bearing while they remain worried about their fertility potential in future. Besides this, I see a lot of women who are not able to conceive and have poor ovarian reserve. Here are seven most frequently asked questions related to “Ovarian Reserve” and my answers to these.

  1. What is ovarian reserve?

Ovarian reserve of a woman is defined as an estimated number of oocytes/ eggs a woman has in her ovaries at a given time. A female fetus has a maximum of 6 to 7 million eggs at 16 to 20 weeks of gestational age. Thereafter, this number keeps on declining and reaches an approximate count of 1 to 2 million eggs at the time of birth, and further falls to approximately  250,000 to 500,000 eggs at puberty. This count further declines to approximately 25,000 at around 37 years of age and to less than 1000 at menopause.

  1. How is ovarian reserve estimated?

There are various tests to assess ovarian reserve. The main tests include –

  1. Serum FSH/LH- done on the 2nd /3rd day of a woman’s menstrual cycle gives an indication of the woman’s egg reserves.
  2. Serum Anti mullerian hormone (AMH) – very sensitive test of testing a woman’s ovarian reserve. It can be done on any day of the menstrual cycle.
  3. Antral Follicle count-  Antral follicle are small follicles present in the ovary that are best seen during the early phases of the menstrual cycle. Transvaginal ultrasound (TVS) of the pelvis is used to count the number of antral follicles, which gives good estimate of the woman’s ovarian reserve.AFC

    3.  Why is testing for ovarian reserve important?

A woman’s ovarian reserve is an indicator of her fertility potential. Women facing difficulty in  conception or planning to delay child bearing should be assessed for their ovarian reserve for timely and appropriate fertility intervention.

  1. What is poor ovarian reserve?

If a woman has a premature decline in her egg quantity due to any reason which reduces her chances of having a mature egg, she is suspected to have “poor ovarian reserve”. It is natural for the number of eggs present in a lady to decline as she ages – both due to ovulation and a natural cell death process called “Apoptosis” – and normally the woman would exhaust her egg reserve by the time she reaches menopause. But, if the decline in egg count happens faster than that and the woman is depleted of her egg reserve before expected menopause, she should be suspected to have “poor ovarian reserve”.

  1. What causes poor ovarian reserve?

Poor ovarian reserve can be caused by a number of reasons-

  1. Genetic defects including chromosomal anomalies such as Turner’s syndrome and gene defects like Fragile X syndrome.
  2. Damage to the ovaries due to any injury, torsion, infection, surgery or due to radiation or chemotherapy.

However in most cases the exact cause of poor ovarian reserve remains unknown.

  1. Does poor ovarian reserve lead to reduced chances of pregnancy?

Poor ovarian reserve is associated with reduced chances of pregnancy both naturally and following fertility treatment. This is because the number of eggs is reduced which corresponds to reduced chances of pregnancy. The goal of ovarian reserve testing is to identify those individuals who are at risk of diminished ovarian reserve so that they can be encouraged to pursue more aggressive treatment to achieve pregnancy.

  1. Is there any treatment to improve the ovarian reserve?

There are no concrete remedies to improve Ovarian reserve however lately some medications have been developed  to improve the egg quality and number. The benefits of these medicines are not yet conclusively proven.

preventing failure

You can read more about management of Poor Ovarian Reserve at

Dr Parul Katiyar 

For more information on poor ovarian reserve and ways to address poor fertility resulting from this, please write to me at


IVF treatment and twins – role of multiple embryo transfer

One of my patients whom I was counselling for IVF treatment for her primary infertility recently asked me a very basic question about the procedure and its outcome. She asked me – “Doctor, can I conceive only twins with IVF?”. This again prompted me to think about this very important aspect of fertility treatment – the risk of multiple pregnancy resulting from multiple embryo transfers. Some big celebrities like Celine Dion, Julia Bradbury and Jennifer Aniston and our own Farah Khan have been in news for conceiving multiple babies with IVF and that somehow makes many women undergoing IVF treatment to think that IVF produces multiple pregnancy only.  In this post, I  will try to explain the reasons for multiple pregnancies resulting from IVF treatment and how can this be avoided.

According to global evidence, approximately 25% of total births resulting from ART treatment are twins, a rate much greater than in the general population (approximately one in 80 births). The incidence of triplets and quadruplets is also high among pregnancies resulting from IVF treatment. However, the majority (approx. 70%) of pregnancies resulting from IVF treatment are singletons. With an ever increasing focus on optimizing treatment outcome and reducing complications associated with IVF treatment, the risk of multiple pregnancies with IVF has become  one of the most important considerations while planning the IVF cycle.

The process of implantation of an embryo in the womb is a complicated one and we still do not know what transpires between the embryo and the uterus when they come in contact with each other, and therefore, we do not completely understand the reasons for a positive or negative pregnancy outcome also. Since there is no test or procedure that can assure pregnancy with IVF – an expensive treatment not generally covered by insurance policies – the physicians naturally want to enhance the probability of pregnancy and consider putting in more than one embryos. The risk of multiple pregnancy in IVF cycle derives from this tendency among treating physicians to transfer more than one embryos inside the uterus in order to increase the odds of pregnancy.

Pregnancy rates with IVF treatment appear to peak with transfer of three or four embryos. However, the risk of multiple pregnancy also increases at the same time. Multiple pregnancy is associated with   a higher rate of maternal, fetal and neonatal complications and is considered as the single biggest risk or complication of fertility treatment.

Good practice in IVF treatment aims to reduce the risk of multiple pregnancy whilst maximizing the overall chances of conception. This is achieved by proper patient selection and counselling.

  1. Young women who have the best chance of conception, also have the highest chance of conceiving multiples. Therefore, I always offer them a single embryo transfer at a time and freeze the rest of the good quality embryos for later use.
  2. An extended culture of embryos up to the day 5, called as blastocyst culture, helps in better embryo selection for transfer into the uterus. I advise blastocyst culture for patients with more than 3 good quality embryos and transfer a single blastocyst in such patients.

I also believe that treating physicians should counsel the 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 to achieve that goal. Patients should be counselled about the risk associated with transferring many embryos and also explained that freezing the spare embryos and transferring them in subsequent cycles if needed  would give them even better cumulative pregnancy outcome than putting back many embryos in one embryos transfer.

Please contact me at for any queries related to IVF or any aspect related to infertility treatment.

Five things to know about Fertility Preservation in women with Cancer

The incidence of cancers among young people is increasing due to changing lifestyles, deteriorating dietary patterns and many other yet unknown factors. And, at the same time newer techniques and technologies allow for early detection and treatment of cancers. A combined effect of these two factors is that more and more women of reproductive age group are now receiving anticancer treatment. While this helps many women lead a longer life, this does not always translate into a high quality reproductive life. Fertility preservation has therefore become very important for such women and they need to know what all options are available for them. This article explains various methods of fertility preservation available for women diagnosed with cancer.

Question 1- What is fertility preservation?

Fertility preservation essentially means preserving the ability of an individual woman or couple to conceive at a later date. These days, women are going for fertility preservation for a number of reasons. These include –

a) Women diagnosed with cancers and being planned for cancer treatment

b) Women undergoing treatment for Rheumatic diseases like Rheumatoid Arthritis and SLE and Myelodysplasia, which require them to take medications which can harm their fertility

c) Social indications – women not wanting to conceive at a young age for reasons such as career aspirations or if they are still looking for a suitable partner

This article discusses fertility preservation for women who are diagnosed with cancers and are going for cancer treatment. Fertility preservation carried out prior to the cancer treatment plays an important role in improving the quality of life of women surviving cancers. We counsel all women of reproductive age group, who are planned for cancer treatment and offer this option to all women who wish to preserve their fertility.

Question 2 – Why should a woman diagnosed with cancer worry about her fertility?

According to the National Cancer Registry of India, the number of newly diagnosed cases of cancer in India will cross the figure of 11 Lakh by year 2020, more than half of whom will likely be women. Of these, approximately two Lakh will be in adult patients within their reproductive years, i.e. up to age of 45 years.

Abdominal surgeries, especially the ones performed for treatment of cancers of reproductive organs – ovaries and uterus can cause permanent damage to the reproductive organs. Similarly, chemo and radiotherapy for cancers also affect the reproductive potential of women, as they have potential to cause genetic and structural damage to the reproductive organs. According to estimates, approximately 40-80% of women receiving cancer treatment are at risk of infertility resulting from cancer treatments in form of chemotherapy, radiation therapy and surgery.

Question 3 – How does cancer chemotherapy affect fertility of a woman?

Chemotherapeutic drugs kill cancer cells by interrupting critical cellular processes and stopping cellular growth and multiplication. But, these drugs can also cause DNA abnormalities and oxidative damage to the normal germ cells (cells which produce eggs) of a woman, leading to death and deformities of developing oocytes. The degree of damage to oocytes depends upon the specific drug that is used and its dose and also on age of the patient receiving this treatment. Older women with relatively lower ovarian reserves are more likely to be affected by the drugs, which can actually lead to premature ovarian failure (POF). The resulting damage to the ovaries can manifest in form of either temporary amenorrhea or premature menopause, both resulting in infertility.

Question 4 – How does radiation therapy affect fertility of a woman?

Radiation therapy can affect both ovary and uterus, thus impacting the fertility potential of the woman. Radiation induced damage to reproductive organs can cause infertility, miscarriage, preterm labor, intrauterine growth retardation and low birth weight. Radiations damage myometrium (inner lining of the uterus), and reduce its blood supply, which cause uterine fibrosis and hormone dependent endometrial insufficiency. The amount of damage caused to the ovaries by radiations depends upon age of the patient and amount of radiation exposure to the ovaries. Over 90% of patients undergoing total body irradiation or total abdominal irradiation eventually end up with ovarian failure.

Question 5 – What are various methods of preserving fertility among women?

There are multiple techniques, which can help women preserve their fertile potential for future and there are some other techniques, which are still emerging. The five main fertility preservation methods are explained below.

1. Embryo cryopreservation

Embryo cryopreservation means freezing embryos for implantation at a later (more suitable) occasion. This requires the patient to undergo IVF before starting the treatment for cancer. The embryos thus formed are then frozen. Embryo freezing is a proven and established technique and offers good results, which of course depend on the number and quality of embryos frozen.

Limitations of embryo cryopreservation:

a) Controlled ovarian stimulation in order to procure the eggs can take between 2-4 weeks’ time, depending on when the patient consults for fertility preservation. This means that the treatment for cancer has to be delayed by that many days, which may not always be in the best interest of the patient.

b) High Serum E2 levels resulting from hormonal stimulation of ovaries may have a negative effect on estrogen-sensitive tumors. We always seek an expert opinion from an oncologist before starting the stimulation.

c) IVF may not be possible in/ preferred by unmarried women, as it required sperms at the time of the procedure, and some women may not want to limit their reproductive autonomy in the future.

d) There are serious ethical and legal implications regarding disposal of the embryos, in case patient dies before she can use the embryos.

e) IVF cannot be used a fertility preservation technique for pre-pubertal girls undergoing treatment for cancers.

2. Mature oocyte cryopreservation

Oocyte cryopreservation (commonly referred to as Egg Freezing) is a preferred method of preserving fertility, especially among unmarried women as it allows the women to maintain their reproductive autonomy in future. However, egg freezing also required the patient to undergo controlled ovarian stimulation and, therefore, suffers from some of the same disadvantages as embryo freezing.

Just like embryo cryopreservation, egg cryopreservation can also not be used to preserve fertility potential among pre-pubertal girls. Also, since only a limited number of eggs/ embryos can be frozen is one cycle, the patient can take only as many attempts at pregnancy in future.

We recommend only one single attempt at stimulation and egg retrieval in order not to delay start of cancer treatment. We also take extreme care during stimulation so as to minimize the chance of ovarian hyper stimulation. The patients undergoing stimulation for fertility preservation are monitored very closely for ovarian response and dose of stimulation is titrated accordingly.

3. Ovarian tissue cryopreservation (OTC)

Ovarian tissue cryopreservation or tissue freezing is the process of harvesting ovarian cortical tissue (containing primordial follicles), dissecting the tissue into small pieces and freezing them for use later on. In most of the cases, this procedure can be performed laparoscopically (key hole surgery) and is done before starting any treatment for cancer. The frozen ovarian tissue can be re-transplanted into the patient on completion of cancer treatment, either into the pelvis (called orthotopic transplant) or in abdominal wall or forearm (called heterotopic transplant).

There is possibility of natural conception with orthotopic pelvic transplant of the ovarian tissue, but the patient definitely needs IVF treatment to conceive after heterotopic transplant of ovarian tissue. We always suggest orthotopic transplantation as a preferred method, as it is more biological and has better success rates.

Indications of Ovarian tissue cryopreservation-

a) Patient age less than 37 years

b) Good ovarian function – S FSH, AFC, AMH

c) Pre-pubertal girls where egg/ embryo freezing is ruled out

d) High risk for Permanent ovarian failure as a result of cancer treatment

Advantages of OTC over egg/ embryo freezing-

a) There is no need to delay cancer treatment in order to do OTC

b) There is no risk of ovarian hyper-stimulation and negative effect of progesterone on cancer

c) Partner or donor sperm is not required at the time of performing OTC, thus woman’s reproductive autonomy is maintained.

d) OTC helps preserve a larger number of follicles and technically allows for the resumption of ovarian function, which may last then many years.

However, OTC is still not a common fertility preserving method, especially for systemic cancers like leukemia, wherein cancer cells may be present in the frozen ovarian tissue. We consider OTC as a fertility preservation technique only in cases where egg/ embryo freezing is not indicated, namely when delaying start of cancer treatment not an option acceptable or controlled ovarian stimulation using hormones is contraindicated or IVF is not possible. OTC does not work for women over 40 years of age, as their ovarian reserve is relatively poor.

4. Fertility-sparing surgery – Ovarian transposition

Patients needing radiation treatment can benefit by fertility sparing surgeries. But, ovarian transposition is not an option for patients needing combined radiation- chemotherapy, which is a case in majority of patients. This procedure involves surgically moving the ovaries away from the field of radiation. For example-

a) Lateral fixation of ovaries in patients needing craniospinal irradiation

b) Moving ovaries out of the pelvis or into the anterior abdominal wall in patients who require radiation therapy to the pelvis

Disadvantages of ovarian transposition-

a) Risk of cyst formation in ovary and postoperative adhesions leading to chronic pelvic pain

b) Some patients may be harboring metastatic cancer in the ovaries, which may skip the radiation treatment

c) Transvaginal ovum pickup is not a viable option if the ovaries have been transposed and the patient may need laparoscopic egg pick up for IVF.

5. In vitro maturation

In vitro maturation (IVM) is another technique of fertility preservation for patients with cancers, but the success rate of IVM remains lower than egg/ embryo freezing. IVM involves aspiration of immature follicles (with/ out hormonal stimulation) for maturation outside of the body. The mature oocytes or embryos thus generated are then frozen for use at a later occasion.

Menstrual irregularities among women

Almost every woman experiences some kind of menstrual irregularities at some point in her life. While there can be many causes for these irregularities, simple remedies are available for most of these women.

Some kind of menstrual irregularity, often accompanied by pain in lower abdomen is one of the most common presenting complaints for a gynecologist.

Irregular period is generally a symptom of some hormonal imbalance (estrogen and progesterone) in the body and is commonly encountered in young girls at the time of menarche (time when a girl starts to have menstrual cycle) and around menopause. Menstrual irregularity can also be seen immediately after child birth or after removal of intrauterine contraceptive device (IUCD). Other common causes include thyroid gland dysfunctions, presence of fibroids or polyps inside the uterus and excessive stress, including examination stress.

mens irreg

It is important to know a few more important details in order to evaluate and understand the same and make any recommendations. These include-

  • Duration of menstrual irregularity
  • Kind of irregularity- interval between two cycles, amount of blood flow and no of days of flow.
  • Any associated pain in lower abdomen.
  • Associated weight gain, growth of excessive facial hair or discharge from nipples.

Early assessment of menstrual disorders also requires an ultrasound scan of lower abdomen to assess condition of uterus and ovaries, specifically to rule out polycystic ovaries (read more about PCOS here), and estimation of following hormone levels in the body – TSH, FSH, LH, Prolactin and testosterone. These blood tests should be done on the second or third day of the periods.

The women experiencing menstrual irregularities should try and manage their weight so as to maintain a BMI of less than 25 Kg/M2. Healthy lifestyle including intake of balanced diet, moderate exercise and avoiding any stress are very useful simple steps every woman can take on their own. In cases with severe irregularity, the woman may be required to get rid of the IUCD, start a birth control pill to regulate the sex hormone levels during cycle and treatment for thyroid dysfunctions, if required.

You can consult with me for more information or treatment for menstrual disorders.

Dr Parul Katiyar

Does infertility treatment put women at higher risk of cancers?

Many patients ask me if IVF treatment leads to a higher risk of cancers, especially in breasts and ovaries. As per the latest published scientific literature on this subject, there is no real evidence to link IVF with higher risk of cancers among these women.

As an infertility specialist, I am required to counsel mcancery patients about potential complications of fertility treatment. One of the most often asked question is if infertility treatments put the women at a higher risk of cancers.

Fertility drugs like clomiphene citrate and hormones used for ovarian stimulation & assisted reproductive technologies like IVF and ICSI have all been implicated to causes various cancers among women, including not only cancers of cervix, uterus, ovaries and breast, but also melanoma and cancers of the central nervous system.

A simple answer to this question is that as per the latest studies, there is no conclusive evidence to suggest a higher risk of invasive cancers in women receiving infertility treatment.

Why has infertility treatment been linked with higher risk of cancers?

There are multiple theories as to why fertility treatment may increases the risk of cancer in women.

  1. Hormonal treatment with Clomiphene and Gonadotropins causes cancers because elevated levels of estrogen and progesterone hormones can trigger carcinogenic activity in the ovarian , uterine and breast tissues
  2. Ovarian enlargement due to development of multiple follicles causes trauma to the ovaries, which may result in carcinogenesis.
  3. Injury to ovaries resulting from multiple needle punctures made during egg retrieval has also been suggested to cause cancers of ovaries.

However, at the same time, it has also been suggested that infertile and nulliparous women are inherently at an increased risk of certain cancers so actually infertility treatment may not be the cause of cancers in these women.

What does the scientific evidence tell us?

Extensive research has been conducted on this subject, but the results so far have been pretty inconclusive. We need to appreciate that it is indeed difficult to study direct relationship between cancers in women and infertility treatment because many of these cancers appear many years after the treatment/ causative injury. Therefore, large populations have to be studied over a long period of time in order to arrive at any meaningful conclusions regarding the relationship between fertility treatment and cancers.

Of all the cancers suspected to be associated with infertility treatment, cancers in ovaries are most often linked to the infertility treatment. The overall evidence in this regard is mixed. While some studies have found the risk of ovarian cancers to be higher in women with a history of fertility treatment, others have ruled any such association out.

A research group from Israel retrospectively studied possibility of such an association in over 106,000 women, who had delivered between 1998 and 2013.1 The researchers found that women with conceived with IVF treatment had a significantly increased risk of being diagnosed with ovarian and uterine cancers as compared to women who had conceived either naturally or using ovulation induction. However, another study of over 87,000 women from Israel only conducted around the same time did not find any significant relationship between IVF exposure and risks of breast, endometrial, or ovarian cancers.2

In a population based cohort study of 812,986 women from Norway, who had delivered between 1984 and 2010, the researchers tried to assess the overall risk of cancers and specifically of cancers of cervix, uterus, ovary, thyroid, the central nervous system and melanoma among the women who had conceived using ART. 3 They found that the overall risk of cancers was not higher among the women conceiving using ART and delivering at least one baby. Although there was a hint of higher incidence of some cancers among women undergoing IVF, this could not be statistically proven owing to the weak nature of this kind of population based study.

A Cochrane review of 25 studies (consisting of 11 case-control studies and 14 cohort studies) covering 182,972 women did not find any convincing evidence supporting an increased risk of invasive ovarian tumors with fertility drug treatment. However, the researchers concluded that there may be an increased risk of borderline ovarian tumors in subfertile women treated with IVF.4

Cancer of the breast is the second most commonly discussed cancer that is assumed to be linked with hormonal treatment for infertility. Large studies and meta-analyses have not found any significant correlation between treatment for infertility and breast cancer. 5,6 While some studies have suggested that the risk of breast cancer increases after exposure to ovulation inducing agents (especially clomiphene citrate)6, many other studies do not support such an association.5 Therefore, I don’t advocate long term administration of Clomiphene, as the risk of breast cancer is not fully ruled out with its long term use.


Overall we can say that on the basis of existing scientific evidence, there is no conclusive proof of a causal link between ovarian and breast cancers and fertility treatment. Therefore, treatment of infertility using hormones and ART is by and large safe. The cancers of ovary and breast detected among women with history of treatment for infertility are more likely to be related to their infertile status than to the effect of fertility drugs. However, we must keep in mind that majority of the available studies on this subject suffer from methodological limitations and therefore cannot be fully relied upon. Further research on this subject will certainly enlighten us more on the possibility of any such association.


1.       The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up. Kessous et al. J Cancer Res Clin Oncol. 2016 Jan;142(1):287-93.

2.       In vitro fertilization and risk of breast and gynecologic cancers: a retrospective cohort study within the Israeli Maccabi Healthcare Services. Brinton et al. Fertil Steril. 2013 Apr;99(5):1189-96.

3.       Cancer risk among parous women following assisted reproductive technology. Reigstad et al. Hum Reprod. 2015 Aug;30(8):1952-63.

4.       Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility. Rizzuto I, Behrens RF, Smith LA. Cochrane Database Syst Rev. 2013 Aug 13;8:CD008215.

5.       IVF and breast cancer: a systematic review and meta-analysis. Sergentanis et al. Hum Reprod Update. Sergentanis et al. 2014 Jan-Feb;20(1):106-23.

6.       Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies. Gennari et al. Breast Cancer Res Treat. 2015 Apr;150(2):405-13.

For further information or queries on this subject, please write to me at

Dr Parul Katiyar

IVF- Frequently Asked Questions – I

Some frequently asked questions about fertility treatment in general and IVF in particular.

In today’s post I am going to address some questions I get asked very often by my patients undergoing fertility treatments, including IVF. I am sure there are many people with similar queries and they will all benefit from this post.

Q 1. Will there be an increased risk of birth defects in my baby if I conceive with IVF?

A. No, there is no merit in such an argument. The risk of birth defects in babies conceived by IVF is the same as for babies conceived naturally. From a scientific perspective, birth defects or congenital anomalies mostly result from alterations in the genetic material (known as mutations) and the process of IVF doesn’t cause any mutations. In fact, the incidence of chromosomal abnormalities such as Down syndrome and Turner’s syndrome with fertility treatment is also same as for general population.

Q 2. Can fertility treatment including the IVF procedure damage ovaries? 

A. There is no real evidence to suggest that either pre-IVF diagnostic laparoscopy or ultrasound guided ovum pickup through vagina causes any major/ permanent physical trauma to the ovaries. These are well established procedures now and carry only as much risk as any other medical intervention/ procedure.

What is more important is the expertise and experience of the treating doctor and quality of equipment and support functions at the treatment facility. So, I encourage my patients to do proper research and due diligence to find out whats the best and most convenient place to seek such treatment.

Q 3. Since IVF can lead to twin pregnancy, should I get only one embryo transferred?

A. It is true that transfer of more than one embryos carries a real risk of twin pregnancy. In fact, as per the collective evidence, the chance of twin pregnancy with IVF is 1 in every 4-5 pregnancies, whereas it is 1 in 80 in naturally conceived pregnancies. The chances of conceiving triplets and quadruplets is also much higher with IVF than naturally. It is also a well known fact that the chance of multiple pregnancy in an IVF cycle goes up as the number of embryos transferred increases.

IVF being a very costly treatment, we need to weigh the risk of multiple pregnancies with the chance of success in a cycle. So, the real questions to ask are how many embryos should be transferred in an IVF cycle and if it is justified to transfer only one embryo during an IVF cycle? While there is no single definite answer to this question, I generally recommend transferring 2-3 embryos – of course, the final count depends upon the quality of the embryos, age of the woman and affordability of the couple seeking IVF.

If the woman treated with IVF actually gets twin pregnancies, I generally advice her to carry on with the same and accept that as God’s gift. However, in case of triplets and quadruplets  I suggest the woman should try selective reduction of implanted embryos in order to increase the chances of successful pregnancy.


Q 4. What precautions should we take after the embryo transfer?

A. As such there are no special precautions to be taken after embryo transfer. The woman can continue with routine diet and regular activities. However, the woman should avoid excessive physical exertion after the transfer. There is also no additional advantage of bed rest after the transfer. I am also often asked if the couple can have intercourse after embryo transfer. While there is no rule regarding this, I advise couples to abstain for two weeks after the transfer just to give some rest to the uterus. 

Q 5. Can we also attempt naturally while going for IVF?

A. Yes, you can because you never know when your prayers get answered! As such there is no medical reason to avoid intercourse while undergoing fertility treatment However, in order to maximize the chances of success with IVF, I recommend that the couple avoids intercourse for 48 hours preceding collection of semen sample to ensure that the semen sample collected for ART is of optimal quality. For the same reason, the male partner should also abstain from masturbating for at least 48 hours preceding sample collection/ egg retrieval.

There are some more frequently asked questions, which I will take up in my subsequent posts.