Highest Success Rates in IVF

“Highest Success Rates in IVF” – Myth or Fact?

Fact (With a Catch!) – IVF success rates can be high, but they vary based on age, clinic expertise, and individual health factors. Some clinics do have above-average success rates, but be cautious of misleading claims.

Common Myths vs. Facts About IVF Success Rates:

Myth: “IVF guarantees pregnancy.”
Fact: IVF increases chances but doesn’t guarantee success. Success depends on factors like egg & sperm quality, embryo health, and uterine conditions.
Myth: “A clinic with the highest success rate is always the best choice.”
Fact: Some clinics may selectively treat patients with a higher chance of success, artificially boosting their statistics. Always check how success rates are calculated!
Myth: “IVF success rates are the same for everyone.”
Fact: Younger women (under 35) have higher success rates (~50% per cycle), while chances decline with age.
Myth: The First IVF Cycle Always Works
Fact: Many couples may need multiple IVF cycles to conceive. Success rates vary per cycle, and persistence often leads to better outcomes.
Myth: Fresh Embryos Are More Successful Than Frozen Ones
Fact: Frozen embryo transfers (FET) can be as successful as or even better than fresh transfers, depending on the individual case.
Myth: IVF Always Results in Twins or Triplets
Fact: Advanced techniques like single embryo transfer (SET) help control multiple pregnancies. Clinics now focus on healthy singleton pregnancies for better outcomes.
Myth: Lifestyle and Diet Don’t Impact IVF Success
Fact: A healthy diet, weight management, and reduced stress can improve IVF outcomes. Avoid smoking, alcohol, and processed foods.

What to Look for in an IVF Clinic?

Transparent success rate reporting by age group.

Use of advanced techniques (ICSI, PGT, embryo freezing).

Comprehensive fertility evaluations before treatment.

📞 Take the Next Step Towards Parenthood!

Visit: www.drabhamajumdar.com

Yoga and Physical Exercises

The Role of Yoga and Physical Exercises in IVF: Benefits and Limitations

Introduction

In-vitro fertilization (IVF) is a complex and emotionally challenging journey for couples struggling with infertility. Many turn to holistic approaches like yoga to improve their chances of success. While Yoga and Physical Exercises offers numerous benefits, it is essential to understand its limitations in the IVF process. This blog explores where yoga helps in IVF and where it may not be effective.

How Yoga and Physical Exercises Helps in IVF?

While Yoga and Physical Exercises cannot replace medical treatments, it can support IVF success in several ways:

Reduces Stress and Anxiety
IVF can be stressful, and stress releases cortisol, which may negatively impact fertility hormones.
It helps reduce stress through deep breathing, meditation, and mindfulness, promoting a calm and positive mindset.
Improves Blood Circulation to Reproductive Organs
Certain yoga poses enhance blood flow to the uterus and ovaries, ensuring better oxygenation and nutrient supply.
Poses like Butterfly Pose (Baddha Konasana) and Legs-Up-the-Wall (Viparita Karani) support reproductive health.
Balances Hormones
Yoga and Physical Exercises regulates the endocrine system, which controls reproductive hormones such as estrogen, progesterone, and insulin.
Women with PCOS (Polycystic Ovary Syndrome) or irregular cycles may benefit from exercise’s hormone-balancing effects.
Enhances Implantation Potential
A relaxed body and mind create a favorable uterine environment for embryo implantation.
Gentle stretching and restorative yoga postures can help improve the uterine lining.
Supports Emotional Well-being During IVF Cycles
IVF can be emotionally draining, with multiple hormonal treatments and waiting periods.
Yoga and Physical Exercises encourages emotional stability, self-acceptance, and positivity, making the process easier to navigate.
Where Yoga and Physical Exercises is Not Effective in IVF?

Despite its benefits, yoga has limitations in treating infertility. It cannot replace medical interventions in the following cases:

Structural Reproductive Issues
Blocked Fallopian Tubes: If tubes are completely blocked, only IVF or surgical treatment can help.
Uterine Fibroids or Polyps: Large fibroids or growths affecting implantation require medical intervention.
Genetic and Chromosomal Abnormalities

Yoga and Physical Exercises cannot correct genetic disorders that may cause repeated IVF failures.
PGT (Preimplantation Genetic Testing) is required to check embryo viability.
Severe Egg or Sperm Quality Issues
If AMH (Anti-Müllerian Hormone) is very low, It cannot increase egg count.
Severe sperm DNA fragmentation or azoospermia (zero sperm count) needs advanced fertility treatments.
Autoimmune Disorders Affecting Implantation
Conditions like lupus or antiphospholipid syndrome can cause repeated IVF failures.
Yoga and Physical Exercises can reduce inflammation but cannot prevent immune attacks on embryos.
Age-Related Infertility
Yoga cannot reverse age-related ovarian decline.
Women over 40 may require egg donation or advanced fertility treatments.

Conclusion

Yoga and Physical Exercises is a valuable supportive therapy that enhances IVF success by improving mental well-being, hormone balance, and blood circulation. However, it cannot treat medical conditions like structural blockages, genetic issues, or poor egg/sperm quality. The best approach is to combine yoga with evidence-based fertility treatments for optimal success.

Must Have High Fibre Foods During Pregnancy

A high-fibre diet is important all the time, but more so when you are pregnant. One of the most important things to remember for your diet during pregnancy is to increase your fibre intake.

Consuming more fibre will help you prevent one of the most common pregnancy symptoms, related to digestive health, that is, constipation. It also helps in managing excessive weight gain during pregnancy. It has many other benefits, like managing the body weight and contributing to your and the baby’s overall wellness. Make sure you consume 25- 30 grammes of fibre daily, while also drinking plenty of water to move it along your system. Here are some fibre-rich foods you can incorporate into your diet while you are pregnant.

1. Whole Grains: Whole grains are a really good way to meet your desired fibre intake goals. This is especially good for people who are only able to tolerate bland foods due to morning sickness or heartburn. There are a lot of whole grains you could add to your pregnancy diet, such as

Oats: Oatmeal is a good source of insoluble fibre and helps in maintaining energy levels by keeping you full for longer. It helps your digestion and prevents constipation. It is also a good source of other micro-nutrients necessary for pregnancy, like zinc, magnesium and folic acid, which are important for foetal development. You can add oats to your diet in the form of oatmeal, granola, and baked goods.
Brown Rice: Brown rice is high in soluble fibre and can help with digestion and constipation. It also contains vitamin B, iron, riboflavin, niacin, thiamine, and vitamin D, all of which contribute to the baby’s growth and development. Eating brown rice is a good way to stay full without consuming too many calories. You can have brown rice as a side dish or in the form of a rice bowl. Brown rice can be chosen instead of polished rice which is an ideal choice to improve fiber intake.
Quinoa: Quinoa is known to give you higher levels of energy. It is rich in fibre, which helps with digestion and can also help you fight chronic illnesses. Quinoa also contains folic acid, a vitamin that is important for foetal growth and proteins. You can add quinoa to your salads or have it stir-fried with vegetables.

2. Legumes: All kinds of beans and legumes are excellent sources of fibre. What is more, they are easy to hide in recipes if you are not a fan of them. You may include the following legumes in your diet:

Lentils: Lentils contain fibre and aid with digestion, while also being a rich source of folate, a vitamin that prevents neural tube defects and reduces the risk of gestational diabetes. Lentils are also a good source of protein and can help you meet your protein intake goals for the day. Consuming protein can ease the pressure on your stomach and relieve some symptoms like morning sickness. You can add different types of lentils to your diet by having dal with every meal.
Chickpeas: Chickpeas are a great source of fibre. They also contain folate, proteins, calcium, and iron. This is another legume you can add to your diet to help you with morning sickness and to meet the fibre requirements. You can add chickpeas to your diet by having hummus, roasted chickpeas, or boiled chickpeas to your salads.
Black Beans: Black beans contain a lot of fibre, which can nourish the microbiome in the gut and stabilise blood glucose levels. Along with that, it also provides you with calcium, proteins, and folate, all of which contribute to the baby’s development. You can add black beans to your diet in the form of rajma curries, tacos, soups, and salads.

3. Fruits: Many fruits are high sources of fibre. The best part is that fruits can help you curb your cravings for sweet things while being a healthy snack.

Apples: Apples are a good source of soluble fibre, which helps with digestion and keeps constipation at bay. Apples also contain antioxidants, which help develop the baby’s cells and tissues and prevent free radicals from entering and damaging the body. You can eat apples by adding them to smoothies and fruit salads.
Pears: Pears are rich in pectin fibre, which helps regulate bowel movements. Pears also have potassium, which is a nutrient which helps in managing blood pressure during pregnancy. It is also a good source of folate and potassium, which helps control blood pressure. Pears can be served fresh or in desserts.
Berries: Berries like blueberries, raspberries, and strawberries are packed with fibre and antioxidants. They are good for the overall health of the pregnant woman. You can eat fresh berries, make smoothies or add them to your cereal or oats.
Oranges: Oranges contain a large number of nutrients that are essential for a pregnant woman. Vitamin C is found in high quantities in oranges and it helps boost your immune system while also preventing cell damage. Folate, another important nutrient for pregnant women, is found in oranges. This helps prevent neural tube defects in babies.
Indian gooseberry: Indian gooseberry or amla is a very good source of insoluble fibre, which is good for improving constipation symptoms. It is also rich in Vitamin C which helps strengthen the immune system and aids in the absorption of iron from food sources.
Guava: Guava is again a fruit rich in insoluble fibre. One serving of guava per day helps in relieving constipation and helps in improving good gut bacteria.

4. Vegetables: It is more important now than ever before for you to consume a few servings of vegetables each day. Some high-fibre vegetables you can consider include the following:

Broccoli: Broccoli is rich in fibre and antioxidants, which help in avoiding constipation and fighting against diseases. It is also high in folate, calcium, and vitamin C. Broccoli is considered to be a superfood for pregnant women. You can have it steamed, stir-fried or in soups.
Carrots: Carrots are high in fibre and have beta-carotene, which is great for vision. This converts to vitamin A, which helps in the foetus’s skin development. You can have carrots in salads, stir-fried or roasted.
Field beans: Field beans are commonly used vegetables in Indian cuisine, enriched with a good amount of fibre. They are also a good source of folate, beta-carotene and potassium. Field beans can be used to make different varieties of vegetable curries.
Drumsticks: Drumsticks are a good source of fibre while being a delicious vegetable to include in your pregnancy diet. Additionally, they are loaded with other micro-nutrients such as folate and vitamin C.
Spinach: Spinach is high in fibre and other nutrients like iron, thereby increasing your energy levels. You can have it cooked or in salads.
Sweet potatoes: Sweet potatoes are a healthy and tasty choice for pregnant women. They are filled with fibre for good digestive health, beta-carotene for the baby’s development, and carbohydrates to provide you with energy for longer. You can add sweet potatoes to your diet in many forms, be it baked or stir-fried.
Green peas: Green peas are a good source of fibre, but they also provide you with protein and folic acid, which is essential for preventing birth defects of the brain and spine.

5. Nuts and Seeds: Nuts and seeds are a great choice for snacking while you are pregnant because of the vast number of nutritional benefits they offer. You can consider the following:

Chia Seeds: Chia seeds are high in soluble fibre to aid with digestion and omega-3 fatty acids. You can add chia seeds to your smoothies, pudding or oatmeal.
Flaxseeds: Flaxseeds are rich in fibre and lignans, which support hormonal balance. It is also a good source of omega-3 fatty acids, vitamins, and minerals. You can sprinkle them on salads and add them as a smoothie topper.
Almonds: Almonds are a good source of fibre, proteins, and healthy fats. They are a great option to snack on when you feel hungry during the day. You can also add it to your salads or in granola bars.
Prunes: Prunes or dried plums are a really good, healthy snacking option for pregnant women. Their high fibre content helps with digestion and constipation. They can also improve your energy levels and reduce anxiety and depression as they have potassium.
Dates: Dates are a good, natural source of fibre and can help with digestion and constipation during pregnancy. They also contain iron, which can help if you have an iron deficiency.
Figs: Figs can provide you with both soluble and insoluble fibre, which helps you deal with constipation. Figs also have potassium to help with blood pressure and hypertension.

6. Other high-fibre snacks

Popcorn: Popcorn is a whole-grain snack that is easy to make and low in calories. You can have it air-popped and lightly seasoned.
Whole grain crackers: Whole grain crackers are a good source of fibre and easy on the stomach. You can have it with many different types of spreads and dips, like hummus, peanut butter, and cheese

7. High-Fibre Breakfast Cereals like Muesli, and Bran Flakes: A breakfast cereal like muesli can help you get a good amount of fibre, however, a word of caution for those who are not used to it, muesli can cause digestive distress. Bran flakes are another good healthy option as they have a high fibre content and can help you beat sugar cravings.

8. Avocado: Avocados are a very good source of fibre during pregnancy. They also contain healthy fats and probiotics, which can help maintain good gut health.

Medically approved by only dietician

Common Pregnancy Myths Busted by Gynecologists

Pregnancy can come with a huge list of do’s and don’ts. With all the different pregnancy advice coming from various sources, it can be hard to keep track of what to follow and what to ignore. So what should you believe? While some bits of advice are correct, like not eating things like sushi, some other advice is more rooted in myth as opposed to fact.

Here, we will try to break down some of the myths so that pregnant women can enjoy some of their favourite things without feeling any guilt. It is still important to check with your doctor if you have any doubts about any of these things. It is also important to remember that every pregnancy is different.

Myth 1: It’s okay to drink alcohol occasionally:

Whether or not you choose to abstain from alcohol completely is a personal decision. However, it is important to remember that several studies link drinking during pregnancy with an increased risk of Foetal Alcohol Spectrum Diseases. Most experts say that pregnant women should avoid alcohol for the entirety of their pregnancies. The birth defects caused by alcohol consumption are entirely avoidable by abstaining from it. Every healthcare provider must make it clear to their patients that no amount of alcohol is safe during pregnancy.

Myth 2: Avoid all caffeine:

Another common myth is that you have to avoid all amounts of caffeine throughout your pregnancy. While it is true that caffeine crosses over from the placenta and reaches the baby, a small cup of coffee every day is completely safe. Having up to 200 mg of caffeine per day is considered to be safe. It is up to you to check if the beverage you are consuming exceeds the accepted amount of caffeine. Generally, one cup of tea or coffee should be okay. Also, watch out for food items like chocolate that have caffeine.

Myth 3: Skip the gym:

If you have heard that exercise is not safe, then you are wrong, you have heard a common myth. According to experts, low-impact workouts can be beneficial for your overall health and well-being during pregnancy. While managing your health, they prepare your body for birth and the baby’s arrival. Exercise can also help you avoid complications like gestational diabetes, preeclampsia, gestational hypertension, and many others. Pregnant women are recommended to get at least 40-60 minutes of moderate exercise every day. Moderation means that the exercise should make you sweat and raise your heart rate, but you should still be able to speak comfortably. As long as you avoid contact sports and exercises that have you lying on your back, you should be fine. Avoid lying on your back at all costs as this shuts down blood flow to the brain and the uterus. Exercise also helps balance your mood and keeps you feeling less stressed. Before starting any new workout routine, make sure you speak to a healthcare professional or doctor.

Myth 4: You should avoid all medications:

A very common myth during pregnancy is that you need to avoid all medications. You do not need to suffer through headaches and colds without medications just because you are pregnant. You should, of course, consult with your healthcare provider before using any over-the-counter medications. Most over-the-counter medications like the ones used for colds, fevers, and acid reflux should be safe to use, but once again, check with your doctor.

Herbal teas and supplements, on the other hand, may not be safe as not enough research has been done on them. The ones you can purchase at the grocery store may be safe, but it is best to check with your doctor before consuming them.

Myth 5: Avoid all seafood:

Another myth related to pregnancy is to avoid all types of seafood. Seafood is actually very nutrient-dense and a great meal choice for when you are pregnant. It is packed with protein and omega-3 fatty acids, iodine, vitamin D, and selenium, all of which are very important for the baby’s development. That being said, not all fish and seafood are good for the baby. It is important to choose fish with low levels of mercury. You can choose options like shrimp, tilapia or salmon. Fish like tilefish, swordfish, bigeye tuna, king mackerel, orange roughy, and shark have the highest amount of mercury and should be avoided at all costs. Sushi should be avoided as well, as pregnant women are told to avoid anything that is uncooked. Raw fish can contain bacteria and parasites that can lead to infection or food-borne illnesses. Cooked sushi rolls like tempura, on the other hand, are safe.

Myth 6: You’re Eating for Two:

This is one of the most popular misconceptions related to pregnancy. While it is true that your baby receives nutrition from you, that does not necessarily mean that you need to eat doubles of everything. In fact, eating twice the amount of what you usually eat can cause pregnancy complications.

Myth 7: Spicy Food Can Induce Labour:

Some people say that eating spicy food can cause gastrointestinal distress, which in turn can induce labour. This is not true. The only thing that may happen from eating spicy food is that you’ll get loose motions or acid reflux. Additionally, loose motions can cause dehydration.

Myth 8: You Can’t Dye Your Hair During Pregnancy:

According to studies, dyeing your hair while you are pregnant is generally considered safe, because a very small amount of chemicals from the dye are absorbed by the skin. Most studies have found that the chemicals found in hair dye are not toxic and safe for pregnant women. However, some other studies suggest that high doses of these chemicals can be dangerous, so you should exercise caution. Keep a window open for ventilation and let your colourist know that you are pregnant.

Myth 9: You Can Predict The Baby’s Gender From Symptoms:

Science has debunked any claims that you can predict your child’s gender based on your pregnancy symptoms. The only way to determine a child’s gender is through an ultrasound scan. Symptoms like the size of your bump, morning sickness, cravings, or the baby’s heartbeat cannot predict the baby’s gender.

Myth 10: You Should Not Fly During Pregnancy:

Usually, it is considered safe to fly during pregnancy, although you should check with your doctor in case you have any complications related to pregnancy. Complications like high blood pressure or the risk of deep vein thrombosis should be checked by a doctor. Moreover, it is only safe to fly up to four weeks before your due date.

There are a lot of incorrect myths out there related to pregnancy and it can be overwhelming. If you have any doubts about what is unsafe during pregnancy, speak to your doctor or healthcare provider.

Medically approved by Dr Abha Majumdar, Director & Head, Emeritus Consultant, Centre of Ivf & Human Reproduction.

Nutrition in Womens Health

Are the nutritional need for women and men same?

Well the nutritional need for women is definitely different from that for men. This is not only because they are different in height and weight but mostly because of their hormonal changes associated with menstruation, childbearing, lactation and menopause, which impose a greater demand of nutrients at different stages of life. The nutrients available for girls and women in a plentiful environment also partly depends upon the dietary habits and prevailing social preferences in a patriarchal society. This often results in women have a higher risk of anaemia, osteoporosis, and various nutritional deficiencies. Apart from societal practices, periconceptionally women need higher amount of iron and calcium apart from other vitamins and minerals a situation which is never there for their male counterparts.

What are the nutritional need for women during conception and peri-conceptional periods (pre conception and post conception while lactating):

Our diet consists of macronutrients like protein, fats, carbohydrates, and sugar and micronutrients like iron, calcium, folic acid, vitamin B complex, selenium, zinc and iodine. Earlier we thought that it is the macronutrient part of our diet which is essential but now we know that the micronutrients play a big part in not only our well-being but also for the child a pregnant women is carrying.

Tips for heathy eating for women pregnant or wanting to conceive:

Do not skip a meal and have early dinner at least 3 to 4 hours before you sleep.

If you want to snack in between meals make fruits or whole grains your snack.

Instead of fruit juice have the whole fruit.

Start you meal with roughage like salad or fruits which have less sugar and let the protein and carbohydrates follow them.

Use more plant based oils for cooking like olive oil, mustard oil or coconut oil.

Include vegetables, fruit, cereals, proteins, and dairy in your meals.

Cook at home more often.

Avoid eating food with added sugar, salt, and trans fats.

In pregnancy and lactation avoid caffeine, nicotine and alcohol.

Get your nutrients primarily from food which you eat and drink rather than from supplements.

Some women might need additional vitamins, minerals, or other supplements at certain times in life like before, after or during pregnancy.

Apart from pregnancy and lactation most girls aged 10 to 20 and women older than 50 need more calcium for good bone health.

Regular exercise regimen or workouts should be a part of our routine to mobilise the calcium you ingest to move it to bones and add to its strength.

Last but not the least; your child is a total parasite when inside your body so all what you eat goes to them may it be the diet you consume or supplements.

Supplements in addition to providing you with the nutrient you require also have colouring agents, preservatives, and carrier agents though in micro quantities which additionally goes to the baby you are carrying or feeding.

Calcium and iron are 2 micro nutrients which the child will take from your stores whether you ingest them additionally in higher quantities or not, and may deplete their stores from the bones or bone marrow if you do not replenish them.

The old saying “you are what you eat” is true. What you eat and drink become the building blocks in your body. Over time, your food and drink choices make a difference in your health.

Role of Specialized Nutrition & critical nutrients in Pregnancy

During pregnancy, specialized nutrition and critical nutrients play a vital role in supporting the health and development of both the mother and the growing fetus. While protein is important, there are several other nutrients that are essential for a healthy pregnancy. Here are some key nutrients and their roles:

Folic Acid:

Folic acid, also known as folate, is crucial for the development of the baby’s neural tube, which eventually forms the brain and spinal cord. Adequate folic acid intake before and during early pregnancy can help prevent neural tube defects. Good sources of folic acid include leafy green vegetables, citrus fruits, beans, and fortified grains

Iron:

Iron is essential for the production of red blood cells and to prevent iron-deficiency anemia in both the mother and the baby. It supports the transport of oxygen to the developing fetus and helps in the growth and development of organs. Iron-rich foods include lean meats, poultry, fish, legumes, and fortified cereals.

Calcium:

Calcium is crucial for the development of the baby’s bones and teeth. It also supports the mother’s bone health. Dairy products like milk, cheese, and yogurt are excellent sources of calcium. Other sources include leafy green vegetables, fortified plant-based milk, and calcium-fortified products.

Omega-3 Fatty Acids:

Omega-3 fatty acids, particularly DHA (docosahexaenoic acid), are essential for the development of the baby’s brain and eyes. They also support the mother’s brain health and may help reduce the risk of preterm birth. Good sources of omega-3 fatty acids include fatty fish (such as salmon and sardines), walnuts, chia seeds, and flaxseeds.

Vitamin D:

Vitamin D is important for bone health and immune function for both the mother and the baby. It helps the body absorb calcium and supports the development of the baby’s teeth and bones. Exposure to sunlight and consuming vitamin D-rich foods like fatty fish, fortified milk, and fortified cereals can help maintain adequate vitamin D levels

Iodine:

Iodine is necessary for the production of thyroid hormones, which are crucial for the baby’s brain development and metabolism. Insufficient iodine intake during pregnancy can lead to cognitive and developmental issues in the baby. Good sources of iodine include iodized salt, seafood, and dairy products.

Vitamin C and Vitamin E:

These vitamins act as antioxidants and help protect the cells from damage. They also support the immune system and aid in the absorption of iron. Citrus fruits, berries, tomatoes, spinach, and nuts are good sources of vitamin C and vitamin E.

It’s important for pregnant women to follow a balanced and varied diet to ensure they obtain these critical nutrients. In some cases, prenatal supplements may be recommended by healthcare professionals to meet the increased nutrient needs during pregnancy. Consulting with a healthcare provider or a registered dietitian is always advisable to personalize nutritional recommendations based on individual needs.

Dinner with the Tatas: Letters from a Frenchwoman document life in Bombay as the 20th century dawned

An excerpt from ‘Marguerite de Bure: Indian Chronicles, Letters from a French Woman in Bombay 1902-1904’, translated from the French by Elsa S Mathews.

Marguerite de Bure (née Rousselet) was born in Orléans, France in 1872. She was the oldest of the five siblings. As a young girl, she grew up reading her uncle Louis Rousselet’s travelogue to India – India and its Native Princes. Inspired by the etchings made by her uncle, she nurtured the dream of travelling to India someday. It is said that she waited till the age of 30 to meet someone who would take her there.

She was introduced to Pierre de Bure, an officer in the French Merchant Navy (Messageries Maritimes) by family friends. They married in 1902 and soon left for Bombay where Pierre was posted for the next two years. In the letters written between 1902-1904, to her family and friends Marguerite documents the lifestyle, customs and social relations that she observes around her.

Controlled ovarian stimulation for IVF in women with advanced endometriosis

1. Why does one have to think differently for controlled ovarian stimulation (COS) in women undergoing IVF (In Vitro Fertilization) with endometriosis?

This is because of many reasons; but two important ones are low ovarian reserve which may occur eithear due to ovarian disease and/or surgery and poor oocyte quality owing to oocytes coming from a diseased and inflamed ovary. Furthermore, the implantation rates and pregnancy rates may also be negatively affected because of impaired endometrial receptivity due to lowered expression of HOXA 10 and ąvβ3 integrins or associated adenomyosis

2. What does one need to consider while developing an ideal protocol for IVF in endometriosis?

The aim of an ideal protocol is to get a good number of high-quality oocytes as well as the best endometrium for implantation. Two standard protocols have been used for controlled ovarian stimulation (COH) for IVF across all continents. The first and the older one is long GnRH-agonist protocol and the second and newer is short GnRH antagonist protocol. However, the second one has replaced the first long protocol in most centres across the world because of its ease of administration, lower number of injections required and a very low complication rate especially regarding the occurrence of ovarian hyperstimulation syndrome (OHSS). Nevertheless, both protocols when used in women in endometriosis have similar IVF outcomes. as the actual impact of GnRH analogues used during COH is on ovarian hormonal control and not on oocyte and embryo quality.

3. Why do we need pre-treatment before COS for IVF in these patients with endometriomas?

Pre-treatment, before starting COH with antagonist protocol, is a good option in all women undergoing IVF to have an equal cohort of gonadotropin sensitive antral follicles. This equalisation of antral follicles naturally happens in women being treated by the long GnRH agonist protocol. However, in women with advanced endometriosis there appears an additional need for further pre-treatment to reduce the inflammatory environment and cytokine excess which is always there due to presence of endometriotic implants. This pre-treatment may consist of either surgical removal of endometriomas or medical treatment which may need to be extended for a few months before COS is initiated.

4. What are the types of pre-treatments which can be given to women with advanced endometriosis before COS for IVF?

The pre-treatment is of 2 types.

Surgical and medical

Surgical pre-treatment is preferred in following conditions:

Endometrioma larger than 4 cm with no previous surgery
Diagnosis of endometrioma in doubt
Large hydrosalpinx with bilaterality
Follicles or ovarian cortex distal to cyst from the vaginal wall and the ultrasound probe
Normal ovarian reserve and young patient

Medical pre-treatment is preferred in the following conditions:

Previous surgery/surgeries for endometriosis
First time endometriomas less than 4cm
Compromised ovarian reserve
Advanced age

5. What medical treatment is already proven to be effective for this purpose and for how long should it be given before starting COS?

Historically, the only medical treatment tried in women with advanced endometriosis had been the prolonged use of depot preparations of GnRH agonist to create very low estrogenic environment which possibly led to better IVF outcome in terms of clinical pregnancy and live birth rates.

Mechanisms of action of prolong GnRH agonist in endometriosis:

Suppression of ovulation reduces exposure of endometriotic implants to a growth factor called midkine in follicular fluid involved in proliferation of endometriotic cells
Direct inhibition of proliferation of endometriotic cells by regulation of apoptotic and angiogenic mechanisms
Inhibition of menstruation reduces exposure to thrombin and its protease activated receptor; factor which leads to cell inflammation
Inhibition of uterine contractions further blocks mechanical stress

Cochrane Database Systemic Review in 2006 by Sallam et al, concluded on the evidence available then, that administration of GnRH agonists for period of 3-6 months prior to IVF or ICSI caused 4-fold increase in clinical pregnancy rate & 9-fold increase in live birth rate. This analysis was based on 3 randomised control trials which included 165 women. After this review the ultra- long protocol was considered ideal for endometriosis as evidence showed statistical improvement in the oocyte quality, embryo quality and implantation rates.

However, contrary to previous findings, the latest Cochrane review done by Georgiou EX et al in 2019 raised questions on the impact of long-term GnRH agonist therapy on the live birth rate and complication rates compared to the regular COS protocols. This review superseded the previous review by Sallam et al done in 2006.

The present Cochrane review compared the prolonged GnRH agonist pre-treatment to no pre-treatment and has been uncertain whether long-term GnRH agonist therapy prior to IVF/ICSI in women with endometriosis affects the live birth rate. The evidence suggests that if the chance of live birth rate is assumed to be 36% with no pre-treatment, the chance following long-term GnRH agonist therapy would be between 9% and 31%. It is also uncertain whether this intervention imparts any benefits regarding complication rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate as well as in the mean number of oocytes and embryos obtained.

Considering the paucity and very low quality of existing data, particularly for the primary outcomes examined, further high-quality trials are required to definitively determine the impact of long-term GnRH agonist therapy on IVF/ICSI outcomes in women with endometriosis.

In 2020 a meta-analysis was published by Cao, X et al. in Reproductive Biology and Endocrinology comparing the ‘Effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometrioses: a meta-analysis’ which included a total of 21 studies in compliance with the standard literature. Randomised and non-randomised trials were analysed separately. Subjects of study were women diagnosed with endometriosis by laparoscopy, laparotomy, or transvaginal aspiration of the ovarian endometrial cyst.

The results showed that GnRH-a ultra-long protocol could improve the clinical pregnancy rate of infertile patients in studies analysed from randomised control trials, especially in patients with stages III–IV endometriosis (RR = 2.04, 95% CI: 1.37~3.04, P < 0.05).

Nevertheless, subgroup analysis found the different down-regulation protocols provided no significant difference in improving clinical outcomes in patients with endometriosis in the non-RCT studies.

6. What are the other medical methods being explored for pre-treatment in women with advanced stage endometriosis undergoing COS for IVF?

Limitations of prolonged down-regulation compel clinicians to avoid using this protocol too often. On one side it is time consuming and delays IVF by 3 to 6 months and on the other side it may over suppress ovaries leading to diminished ovarian response especially in poor responders. Therefore, other medical methods are being explored to minimize negative effect of endometriosis on oocytes.

Dienogest for 3 months prior to COS
Oral contraceptive pills for 6 to 8 weeks prior to COS
Two monthly doses of injectable GnRH agonist depot with letrozole for 2 months as pre-treatment

Dienogest as pre-treatment:

Dienogest is a progestogen with no estrogenic activity. In addition, it also has anti-inflammatory and anti-angiogenic activity, and it is felt that its prolonged use may lead to better implantation rates. To see the benefit of this drug as a pre-treatment agent before COS in women with advanced endometriosis undergoing IVF, retrospective analysis of prospectively collected database of 151 women was done. These women had failed a previous IVF cycle and all subsequent embryo transfers and had an imaging diagnosis of endometriosis. Patients either underwent IVF without receiving hormonal treatment or received 3 months of treatment with DNG (2 mg/daily) before COS for IVF. All patients receiving DNG were assigned to long protocol with 21 days of daily GnRH agonist administration in the last 3 weeks of the 3-month pre-treatment and were also kept dienogest free in last 2 weeks before starting COH.

The results showed that the largest diameter of endometriomas significantly decreased after DNG pre-treatment (P < 0.001). The use of DNG also increased the number of oocytes retrieved significantly (P= 0.031), two-pronuclear embryos (P = 0.039) and blastocysts (P = 0.005) in women with endometriomas of diameter ≥4 cm.

This study suggests that in patients with endometriosis, IVF outcomes can be improved by pre-treatment with DNG. In particular, the use of DNG allows for better oocyte retrieval and blastocysts conversion in patients with large endometriomas. The cumulative implantation, clinical pregnancy and live birth rates were significantly higher in the DNG-treated group.

Oral contraceptive pills for 6 to 8 prior to COS:

It has been speculated that long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis. Alternatively, IVF/ICSI pre-treatment with continuously administered oral contraceptives may offer fewer side-effects and lower indirect costs, as well as encouraging IVF outcomes in women with endometriosis. To date, these two different IVF/ICSI pre-treatment strategies in women with endometriosis have not been directly compared.

A study has been designed with the title ‘Continuous oral contraceptives versus long term pituitary desensitization prior to IVF-ICSI in moderate to severe endometriosis: A non-inferiority randomised controlled trial’. in an open access publication in Human Reproduction Open. pp 1 to 8. 2019. The sample size calculation is rounded off to 165 patients per group; 330 patients in total will be included. After informed consent, web-based block randomization will be stratified per centre. The protocol for this study has been laid down which is expected to be complete in 3-5 years. This study aims to see and compare the effectivity of OCP pre-treatment in an open-label, parallel two-arm randomized controlled. multicentre trial, which will only include patients with moderate to severe endometriosis.

GnRh agonist with letrozole:

The use of 2 drugs has been analysed in a trial titled ‘A comparison of 2 months of pre-treatment with GnRh agonist depot with or without the addition of letrozole in women undergoing IVF with ultrasound diagnosed endometrioma’ by Arielle Cantor and published in volume 38 issue 4 in RBMO 2019.

To answer the question that, does the addition of an aromatase inhibitor improve IVF outcomes in women with endometriomas when pre-treating them with gonadotrophin-releasing hormone agonists’, a retrospective two-centre cohort study was analysed. This analysis was done for 126 women aged 21–39 years who failed a previous IVF cycle and all subsequent embryo transfers and had sonographic evidence of endometriomas. Women were non-randomly assigned to either 3.75 mg intramuscular depo-leuprolide treatment alone or in combination with 5 mg of oral letrozole daily for 60 days prior to undergoing a fresh IVF cycle. Main outcome measures included clinical pregnancy rate and ongoing pregnancy rate after 24 weeks’ gestation. Prior to treatment, antral follicle count (AFC), basal serum FSH and endometrioma diameter did not differ between groups. After treatment, AFC differed between letrozole and non-letrozole-treated groups (10.3 ± 2.0 versus 6.4 ± 2.5; P = 0.0001), as did mean endometrioma maximum diameter (1.8 ± 0.4 cm versus 3.2 ± 0.8 cm; P = 0.0001). At IVF, the gonadotrophin dose used was significantly lower in letrozole-treated subjects (2079 ± 1119 versus 3716 ± 1314; P = 0.0001), the number of mature oocytes collected was greater (9.1 ± 2.4 versus 4.0 ± 1.7; P = 0.0001), as were the number of two-pronuclear embryos and number of blastocysts. The clinical pregnancy rate was significantly higher in the letrozole-treated group (50% versus 22%, P = 0.003), as was the live birth rate (40% versus 17%, P = 0.008).

Therefore, it looks worthwhile to try the combination of depo-leuprolide acetate monthly for 60 days with daily letrozole for the same duration in women with endometriomas rather than depo-leuprolide acetate treatment alone for 2 months.

7. What is the message for women with advanced endometriosis undergoing COS for IVF?

1. COS for IVF in women with endometriosis is like those without endometriosis and dose of gonadotropin and protocol depends on the age, ovarian reserve, and previous response to stimulation.
2. Attention is now focusing on pre-treatment in women with high stage endometriosis to reduce the proinflammatory detrimental effect of the disease on oocyte, embryo, and endometrium.
3. The first drug used for this purpose was depot GnRh agonist for 3 to 6 months. However, a plethora of newer cost effective and easy to administer drugs are being tried with the same aim of reducing proliferation, vascularization, and inflammation of these endometriotic implants.
4. IVF appears to be first choice of treatment in women with advanced endometriosis desiring conception and have been trying to conceive seriously over a period. Medical treatment should only be used as pre-treatment to IVF and surgical treatment only if mandatory.

References

1. Cochrane Database Systemic Review .2006(Jan);1:CD004635. Salem et al;
2. Georgiou EX, Melo, P, Baker PE, Sallam HN, Arici A, Garcia-Velasco JA, Abou-Setta AM, Becker C, Granne IE. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis 2019 10.1002/14651858.CD013240.pub2; Cochrane Database of Systematic Reviews.
3. Cao X, Chang HY, Xu JY, Zheng Y, Xiang YG, Xiao B, Geng XJ, Ni LL, Chu XY, Tao SB, He Y, Mao GH. The effectiveness of different down-regulating protocols on in vitro fertilization-embryo transfer in endometriosis: a meta-analysis. Reprod Biol Endocrinol. 2020 Feb 29;18(1):16.
4. Fabio Barra, Antonio Simone Laganà, Carolina Scala, Simone Garzon, Fabio Ghezzi, Simone Ferrero, Pre-treatment with dienogest in women with endometriosis undergoing IVF after a previous failed cycle, Reproductive Bio Medicine Online, Volume 2020; 41(5):859-868.
Cantor A, Tannus S, Son WY, Tan SL, Dahan MH. A comparison of two months pre-treatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF. Reprod Biomed Online. 2019 Apr;38(4):520-527.
6. van der Houwen LEE, Lier MCI, Schreurs AMF, van Wely M, Hompes PGA, Cantineau AEP, Schats R, Lambalk CB, Mijatovic V. Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis: study protocol of a non-inferiority randomized controlled trial. Hum Reprod Open. 2019 Feb 23;2019(1):hoz001.

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