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.

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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.

Conclusion

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.

References

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 ivfgurgaon@gmail.com.

Dr Parul Katiyar

Birth control pills and Infertility

One of the most common myths around infertility is whether past usage of birth control pills by a woman can result in infertility later on. If you also have a similar query, please read on for an answer!

Many women with suspected/ diagnosed infertility often ask me if their infertility could have resulted from usage of birth control pills in the past. There is clearly no such association between using birth control pills and infertility and suppression of fertility by birth control pills gets completely reversed on discontinuing the pill. Let us first understand how the birth control pills actually work, and, then we will discuss why these pills cannot lead to infertility.

History of birth control pill

Birth control pills have been in existence since year 1957, when the US FDA approved using these hormonal tablets for treatment of severe menstrual disorders. However, they became much more popular some three year later, when the same US FDA approved using these pills as “birth control pills”. Over these 55 years, this magical medicine has been safely used by millions of women all over the world to control when they want to be mothers, and therefore, have been touted as a “woman’s best friend”.

The pills have evolved over all these years and the new generation birth control pills, which are uses these days contain much lesser quantity of hormones than their original predecessors. This makes the modern pills much safer for women, while being equally efficacious in preventing ovulation and controlling the menstrual cycle.

How do birth control pills work?

Birth control pills are essentially hormone pills containing female sex hormones – estrogen and progesterone. These hormones send negative signals to the pituitary gland located within the brain, thus stopping production of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. FSH and LH are responsible for maturation of a growing follicle and ovulation during the normal menstrual cycle. Circulating FSH and LH do not allow the uterine lining to grow appropriately. This, in turn, leads to formation of abnormal cervical mucus, which inhibits swift movement of sperms and also doesn’t allow the embryo (if it forms) to settle in the endometrium.

Can use of birth control pills lead to infertility?  

The simple answer is “No”, because the pill just contains the synthetic version of the hormones which are otherwise also produced inside the woman’s body!

There is now enough scientific evidence to refute any cause- effect relationship between intake of birth control pills and subsequent infertility. Some temporary disruption in menstrual cycle for a few months after stopping the pill is known to occur in some women and is known as “post-pill amenorrhea”. But even this phenomenon is mostly unrelated to intake of pill per se and is rather caused by coexisting problems such as being underweight or depressed. Most of the women resume their normal “pre-pill” cycles within 1-3 month of stopping the pill and are ovulating normally by this time.

What are the benefits of using birth control pills for subfertile women?

Birth control pills provide some additional benefits to enhance fertility among women.

  1. In women with irregular cycles, especially due to polycystic ovaries (PCOS), birth control pills are used to improve hormonal imbalance as a premedication before starting fertility treatment. Read here for more information on PCOS and infertility.
  2. Birth control pills are very useful in managing the excessive facial hair growth (hirsutism) in patients with PCOS. The pills suppress the level of circulating male hormones in the body of these patients, which is the major cause of facial hair growth. Read more about hirsutism and role of birth control pills in its treatment here.
  3. Birth control pills also provide some protection against Pelvic Inflammatory Disease (PID) – an infective condition of the female reproductive organs leading to inflammation and blockage of tubes. The pills cause thickening of cervical mucus, which protects the reproductive organs from infections by preventing transport of infective organisms into uterus and tubes. You can read more about PID and infertility in my upcoming post.
  4. Birth control pills help in improving the symptoms of endometriosis, especially the pain associated with it. Using the pills also slows down the progression of the disease by reducing the level of circulating estrogen in body. I will be writing on this subject soon.
  5. Intake of birth control pills is also known to reduce the risk of cancers of ovaries and uterus, which themselves could affect the woman’s fertility.

Are there any risks associated with use of birth control pills?

Birth control pills falls under the category of “Schedule H” drugs in India, which means that a physician’s prescription is required to purchase these pills. Irrespective of this regulations and like for any other medication, birth control pills should always be started only on a doctor’s advice. Although the modern pills are very safe and have minimal side effects/ complications in vast majority of users, there are situations in which the pills should be used with caution/ not used at all, such as women over 40 years of age, smokers, women with known liver diseases or clotting disorders etc. Please read more about such contraindications in the suggested readings below and consult your gynecologist before starting the pill.

Further readings

  1. https://www.plannedparenthood.org/learn/birth-control/birth-control-pill
  2. http://www.webmd.com/sex/birth-control/birth-control-pills?page=1#1
  3. http://www.mayoclinic.org/tests-procedures/combination-birth-control-pills/basics/definition/prc-20014056

Making IVF Patient Friendly with Milder Stimulation

It is time to adopt more physiological and patient friendly ovarian stimulation strategies for IVF, which require lesser amount of hormonal stimulation and still produce 2-3 follicles for IVF. Such minimal/ mild stimulation protocols should preferably be used in the modern infertility practice.

There has been good debate on what is the correct number of eggs to be retrieved and number of embryos to be transferred during an IVF cycle. The debate revolves around success rate and cost of the procedure and patient comfort and compliance. I will try to address the first of these two questions, i.e. whats is a good number of eggs to retrieve during an IVF cycle and how should one go about it.

Technically speaking, a single egg has the potential for fertilization and the first IVF baby was born from a natural cycle IVF. But, not every egg gets fertilized on being exposed to sperms and not all embryos have the potential to result in a pregnancy. This inherent failure of assurance of pregnancy resulting from the transfer of a single embryo (fertilized egg) after IVF has resulted in evolution of the practices of artificially inducing the ovaries to produce many eggs in a cycle and of transferring more than one embryo into the uterus. However, even these interventions do not guarantee success of the IVF cycle and the outcome of such IVF cycles can also be measured only in terms of probability.

What is the standard IVF practice?

The standard practice is to give daily hormonal injections to induce the growth of many eggs (targeted number of eggs varies from 5-6 to up to 10), which is coupled with strict monitoring using ultrasounds and blood tests. This process is often very stressful and unfriendly for the patient. This also entails a risk of some complications due to the stimulation which can be short term and may have some long term sequel as well.

What are the disadvantages of conventional stimulation protocols for IVF?

The conventional stimulation protocols have following disadvantages-

  1. Patient discomfort associated with daily injections
  2. Risk of complications like ovarian hyperstimulation, which occurs as a result of recruitment of excessive number of follicles.
  3. In patients with poor ovarian reserve, higher dosage of hormones may not yield more eggs because stimulation helps in recruitment of follicles already present in the ovaries.
  4. Quantity does not correlate with quality – Retrieval of a larger no of eggs may not necessarily mean better quality of eggs. In fact, many of these eggs may be of poor quality and some may even have aneuploidy.
  5. Excessive production of hormone Estradiol (produced by a larger no of growing follicles) has a negative impact on the endometrial receptivity, i.e. the ability of endometrium to allow implantation of the embryos. This may negatively affect the outcome of the cycle.

 

Standard ovarian stimulation – Growth of multiple follicles

What is minimal/ mild stimulation IVF?

Minimal/ mild stimulation strategy aims to optimally stimulate the ovaries to produce a few (typically 2-7) follicles, rather than bombarding them with hormones in order to produce a larger numbers of follicles. This strategy yields a smaller no of follicles, but these follicles are optimally primed to grow and are likely to be healthier. These protocols use either only oral medications or a combination of oral medications and lower dose of hormones given for a shorter duration. Mild stimulation strategies are specially beneficial for IVF in women, who are at higher risk of hyper-stimulation or are known poor responders.

What are the advantages of minimal/ mild stimulation IVF?

Minimal/ mild stimulation IVF, sometimes also called as micro IVF or mini IVF offers several advantages to select group of patients. These include-

  1. The minimal/ mild stimulation protocols are more patient friendly as they require relatively lesser medical intervention.
  2. Minimal/ mild stimulation is more physiological and in sync with woman’s natural cycle.
  3. Growth of lesser number of follicles means a less steep rise in the levels of hormone Estradiol, as a result of which endometrium is likely to be more receptive, thus achieving good pregnancy rate despite of lesser number of eggs.
three follicles
Minimal ovarian stimulation – growth of three follicles

This is the time to reconsider ovarian stimulation strategies for IVF, so that a good pregnancy rate can be balanced with more physiological and patient friendly treatment.

Further Readings

1. http://humrep.oxfordjournals.org/content/25/11/2678.full

2. http://www.ncbi.nlm.nih.gov/pubmed/19091754

Living with PCOS- Survival Kit!

The affected woman has to take the ownership of her treatment in order to beat PCOS.

How to tackle PCOS?
How to tackle PCOS?

         If you are one of those 30% of women having PCOS, then this is your space! 

PCOS is a very common, yet often misdiagnosed condition and many women will call themselves as polycystic ovarian disease (PCOD) or polycystic ovarian syndrome (PCOS) without knowing its full meaning and implications.

What is PCOS?

It is important to understand that PCOS is not a disease, but a syndrome- which literally means that it is a group of symptoms resulting from involvement of multiple systems of body. It can affect anyone from a young adolescent girl to an adult woman even beyond a woman’s reproductive age. The name polycystic ovary is derived from the typical appearance of the ovaries, wherein multiple small cyst like spaces can be seen inside the ovaries. But, one must understand that this polycystic appearance of the ovaries is an outcome of the syndrome rather than being a cause for that. The PCOS can present in many ways, which can range from common symptoms such as weight gain, acne, facial and excessive body hair (hirsutism) and irregular menstruation to very serious medico-social issues such as infertility, diabetes, hypertension and uterine cancers.

Polycystic ovaries
Polycystic ovaries

So, how does one suspect if she is having PCOS?

PCOS can manifest for the first time right at puberty. The affected girls may gain a lot of weight all of a sudden and may continue to struggle controlling weight for many years. Weight gain could be accompanied by menstrual irregularities, facial hair and acne, besides many other similar symptoms. While diagnosing PCOS at this stage can be really tricky because there is no single test that’s diagnostic of this condition, most of the symptoms described above can actually be controlled with help of oral contraceptive pills. However, when these women on birth control pills start planning a baby and have to stop taking the pills, many of them discover that they are unable to conceive. Consultation with an expert is very helpful at this stage, as the expert can correctly diagnose the problem and also advise on the best way to manage the symptoms. But, the affected woman has to take the ownership of her treatment in order to beat PCOS. This would include maintaining an active lifestyle with regular exercise and having a low carbohydrate diet in an effort to keep the weight under check. These interventions go a long way in controlling the symptoms of PCOS, as weight gain initiates a vicious cycle of further hormonal imbalance, which in turn leads to more weight gain. Lifestyle correction coupled with appropriate use of medications to reduce the insulin resistance is the best way to manage PCOS.

What if one gets diagnosed with PCOS? Is it over for her now?

Most common question that I get asked is if PCOS can be cured? Very sadly the answer is No- PCOS cannot be cured! But, the symptoms of PCOS can most certainly be controlled using appropriate medical treatment and lifestyle interventions described above. The key to control of these symptoms is diagnosis at an early age and well titrated intervention from an expert. Remember that it is a condition of hormonal imbalance in the body, which results in irregular ovulation, over production of male sex hormones and resistance to the action of insulin. So, in very simple words, all the interventions would be focused on correcting this hormonal imbalance in the body.

So, what can be done to manage infertility in PCOS patients?

Most women with PCOS are able to overcome the challenge to their fertility with proper treatment. This treatment may vary from simple measures such as oral tablets to induce ovulation to IUI and all the way to IVF. One should always seek an expert’s opinion for management of PCOS when planning for a baby, as the doctor is the best person to support in this endeavor. Always remember that PCOS stays with the woman throughout her journey of life and she has to remain vigilant to identify its long term risks such as diabetes, hypertension and uterine cancers in their early stage!

Reading resources

You can use the following resources to understand more about PCOS, its implications and treatment options-

1. http://www.patient.co.uk/health/polycystic-ovary-syndrome-leaflet

2. http://www.uptodate.com/contents/polycystic-ovary-syndrome-pcos-beyond-the-basics

3. http://www.hormone.org/patient-guides/2014/pcos

Alternatively, you can write to us at ivfgurgaon@gmail.com with your queries.

Mind your weight so you don’t have to wait!

Mind your weight so you don’t have to wait!

An anxious, overweight woman came in to consult me a couple of weeks back. She has been trying to conceive for two years but has been unsuccessful. Now she has not had her menses for last 9 weeks but her pregnancy test was negative. She has been having her periods irregularly for last many years.

A rapidly growing and often ignored problem

The number of young overweight women and men seeking medical assistance for planning family is on a rise. Being overweight not only affects ones’ chances of becoming a parent, but also can lead to complications in pregnancy- adversely affecting both mother and baby.  Therefore, it is very important for all young men and women to know the fundamentals of causation and detection of this important disorder.

Mind your weight so you don’t have to wait!

When to be concerned?

The most often asked questions in this context are- what is a normal acceptable weight, when does one get labelled as overweight and what is the definition of obesity? Another important question we often get asked is- what’s the difference between being overweight and obese? In very simple terms, what a physician evaluates to check for obesity in a person is a simple index known as “body mass Indexor BMI. BMI can be calculated by simply dividing the person’s body weight in Kg by the square of person’s height measured in meters.

BMI is measured as Kg/m2

In very simple terms, a BMI of 18-24 is considered to be normal and anyone having a BMI beyond this range is either overweight or obese. Many simple calculators to measure one’s BMI are freely available on internet. You can try one of the following links to check your BMI-

The following are broad guidelines for detection of obesity-

  • BMI of < 18.5 indicates that the person is underweight
  • BMI between 18.5 and 24.9 indicates that the person has got normal weight
  • BMI between 25 and 29.9 indicates that the person is overweight
  • BMI of > 30 indicates obesity

How does Obesity affect fertility?

Excessive body weight in women causes multiple hormonal imbalances, which can result in irregular menstruation and reduced frequency of ovulation, thus leading to infertility. Also, the outcome of Infertility treatment in obese women is poorer than in their normal weight counterparts. Obesity also increases the chances of pregnancy related complications such as miscarriage, pregnancy induced hypertension and gestational diabetes and hence increases the requirement offers cesarean delivery. And not to forget that the labor is that much harder and prolonged for obese women.

Obese males also suffer from reduced fertility as they tend to have lower level of testosterone, which suppresses sperm production. Obesity can also case erectile dysfunction in men, which can result in reduced fertility.

What can you do?

So, what to do if you are struggling getting a baby and have been diagnosed as overweight or obese? Here are five easy weight management tips to help you realize your dream of having a child-

  • Watch your meals- take a healthy diet and avoid excess carbohydrates and fat
  • Watch your beverages- drink adequate quantity of water, avoid soft drinks as they contain empty calories and refrain from alcohol
  • Stop smoking and keep in mind that there is nothing like occasional/ moderate smoking
  • Exercise regularly and maintain a healthy, active lifestyle- short sessions of brisk walking, swimming, jogging or skipping are good means to keep one active and healthy
  • Avoid stress and practice Yoga/ meditation or other stress buster techniques that suit you

Want to know more or seek an expert opinion, write to us at ivfgurgaon@gmail.com today!