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 ivfgurgaon@gmail.com 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 ivfgurgaon@gmail.com if you have any questions about IVF.

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 ivfgurgaon@gmail.com 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 http://www.slideshare.net/DrParulKatiyar/management-of-poor-ovarian-reserve-dr-parul-katiyar

Dr Parul Katiyar 

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

 

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 ivfgurgaon@gmail.com for any queries related to IVF or any aspect related to infertility treatment.

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.