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.

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.