Assisted reproductive technology (ART) is a medical science which helps couples who are unable to conceive, or singles who want to have biological children, live their dream. ART covers a wide spectrum of treatments, In Vitro Fertilization (IVF) being the most common one among others. The IVF process involves extracting eggs from a female body, fertilizing these eggs with male sperms in a laboratory, fructifying the resultant embryo, and implanting it in the female body to effect a pregnancy. However, many women fail to become pregnant after this procedure. Pre-implantation genetic screening (PGS) is a technique that can be used in conjunction with IVF to improve pregnancy rates and also the resultant number of healthy births.

During an IVF procedure, embryos are developed in the laboratory by fertilizing the female eggs with male sperms. An embryo that contains a normal number of chromosomes i.e. 23 pairs of chromosomes in each cell, is called a ‘euploid’ embryo. An embryo that carries an abnormal number of chromosomes is ‘aneuploid’. Examples of aneuploid embryos include those with 18 sets or 21 sets of chromosomes, or maybe a single additional or missing chromosome resulting in a total of 47 or 45 chromosomes instead of the usual 46. Pre-implantation genetic screening (PGS) is a technique used to identify the number of chromosomes present in embryos created through IVF. After PGS, only embryos with a normal number of chromosomes i.e. the genetically healthy embryos are used and furthermore, the good looking ones among these are used for implantation in the uterus. These embryos are considered potentially competent to propagate viable pregnancies and thus help increase the success rate per transfer.

Practitioners in the field of ART recommend PGS of embryos prior to the implantation process, citing financial, physical and most importantly emotional well-being for the hopeful couples or singles undergoing the treatment:

  • PGS gives a statistical basis to the hope of people undergoing treatments, with regards to a achieving a successful pregnancy. For example, if the couple is informed by their practitioner that in their case 20 eggs fertilized into 15 embryos. Of these 15 embryos, only 8 reached the blastocyst stage and could be sent for PGS, and out of those 8 only 3 were reported normal and could be used for implantation. Here, the couple would place their hopes not on the 15 embryos fertilized, but on the 3 that could result in a successful pregnancy. Realistic hopes versus high hopes can make a huge difference to the emotional impact of a failed pregnancy.
  • PGS can help avert the risk of multiple pregnancies in a client, which usually happens when 2-3 embryos are implanted in a single cycle to increase the chance of achieving a pregnancy. The client can achieve success with single embryo transfer cycles for the select number of competent embryos identified through PGS.
  • PGS can help avert the emotional and physical turmoil of a patient, resulting from a miscarriage caused due to implantation of an embryo with abnormal chromosome count, weeks after soaking in the happiness of achieving a successful IVF pregnancy.

However, investigation has also revealed that PGS, though an excellent tool to improve implantation success rates, is not a panacea when it comes to identifying ‘competent’ embryos. There are factors other than numerical chromosomal integrity that influence embryo “competency”, profoundly.

Advancing age of a woman is a key factor contributing to an increase in the incidence of abnormal embryos. For women less than 36 years of age, roughly 50% of the embryos would most likely be competent. Conversely, for a woman in her mid-forties, the chance of an embryo being competent would probably be just around 10-12.5%.

Independent of embryo competency, there are other variables that also determine IVF outcome. These include selection and implementation of protocols for controlled ovarian stimulation (COS), endometrial factors that determine embryo implantation, technical skill of the physician performing embryo transfer etc.

Also, a limiting factor of PGS is the need of embryos to be cultured for 5-6 days until a blastocyst stage is reached, which can then be biopsied and sent for genetic analysis. However, it is well known that some healthy embryos don’t advance to the blastocyst stage. Younger patients have many embryos that will progress to the blastocyst stage, however older patients with fewer eggs and embryos have a lesser opportunity to reach the blastocyst stage.

So in the case of a patient with advanced maternal age who has few embryos available at day 3 (prior to the blastocyst stage) a decision has to be made either in favour of transferring the embryos on day 3 or culture them further with the risk that they don’t make it to the stage where biopsy can be conducted on them.


Oocyte Cryopreservation directly translates as ‘Egg Freezing’ in common man’s language. Human Oocyte cryopreservation is a process in which a woman’s eggs (oocytes) are extracted, frozen and stored, as a method to preserve reproductive potential in women of reproductive age.

An oocyte is an immature egg cell which eventually matures to become an ovum or egg. This egg is then released during ovulation, a process which occurs once, mid-way through a female’s monthly cycle. If a sperm meets and fertilizes the egg, an embryo is formed else the egg is discarded resulting in menstruation.

A woman is born with all the oocytes (eggs) that she will ever have – approximately 2 million or less. At puberty, when she develops the hormonal capacity to take the eggs to complete maturity, the number of eggs remaining is already down to 300,000. Though she will only need 300 to 400 eggs in her lifetime, but by her mid-30s, the eggs that remain are of lower quality, as the best and most responsive eggs have already matured and died in the absence of fertilisation. Thus a woman’s increasing age effects a decline both in the probability and quality of her fertility.

Human Oocyte Cryopreservation or Egg freezing helps a woman preserve quality eggs which mature in her 20’s, and use them in the future to have biological children when is ready for them. This helps her take control of her life and not rush to start a family because the biological clock is ticking away.    

The Oocyte Cryopreservation technique involves four key steps:

  • The woman has to undergo one to several weeks of hormone injections that stimulate her ovaries to ripen multiple eggs;
  • The eggs are subsequently removed from the body;
  • The eggs are frozen using a flash-freezing process known as vitrification;
  • The frozen eggs are transferred to a liquid nitrogen storage chamber for storage.

Statistics, though limited, suggest that the eggs have the same chance of becoming a baby when frozen and used later, as they would if freshly fertilized and used in an IVF cycle. However, that chance is determined by the woman’s age at the time of freezing the eggs. The highest live birth rates from previously frozen eggs are shown to have come from women who froze their eggs in their early 20’s or before they turned 30. Hence, to achieve a high probability of success at a live birth in the future, it is advised that women wanting to freeze eggs do so in their 20’s or best before the age of 36.

Oocyte Cryopreservation is advisable for:

  • Women diagnosed with cancer:
    • In case of women suffering with cancers of the reproductive system, the treatment might involve surgery to remove a crucial part of the reproductive system thereby making it impossible for the woman to conceive on her own.
    • In other cases of cancer, surgeries, chemotherapy and radiation treatments can cause toxic damage to the oocytes hampering the woman’s fertility.
  • Women undergoing treatment with assisted reproductive technologies like IVF, and object to embryo freezing for ethical or religious reasons;
  • Women with medical reasons like a family history of early menopause, endometriosis, PCOS etc.;
  • Women who have not yet found their ideal life partner with whom they would like to start a family.

However, Oocyte Cryopreservation is becoming increasingly popular with progressive urban women who want to consider marriage and pregnancy at a later stage in life due to education or career priorities, or becoming financially sound, or just any personal reason. ‘Social egg freezing’ is a term coined to describe this practice of freezing a woman’s eggs for non-medical reasons. This is also referred to as ‘Elective Oocyte Preservation’.


Repeated implantation failure (RIF) or Recurrent IVF failure is considered when embryos transferred to the uterus, fail to implant following several In vitro fertilization (IVF) treatment cycles. Though, there is no formal criteria defining the number of failed cycles or the total number of embryos transferred in these IVF attempts. However, we recommend defining RIF as failure of implantation in at least 4-5 consecutive IVF attempts, in which 1–2 embryos of high grade quality are transferred in each cycle. The causes of RIF may be varied and may involve any of the following factors:

    • the egg,
    • the sperm,
    • the embryos created,
    • the uterus,
    • maternal and paternal health, or
    • combination of any of the above listed factors.

The Egg: The quality of a woman’s eggs plays an important role in creating a healthy embryo. As maternal age advances, the percentage of chromosomally abnormal eggs (aneuploidy) increases, reducing the chance of creating a healthy embryo naturally. There are several solutions to counter this concern – Egg freezing technology can be opted for preserving the healthier eggs available before a woman attains 35 years of age; else stimulating drugs can be used to obtain more eggs to help develop more embryos and with Pre-genetic screening technology (PGS) the healthiest embryos can be identified for implantation; egg donation can also be considered as an option.

The Sperm: The sperm plays an equally important role in the formation of a healthy embryo, by transmitting a healthy DNA to the egg. In some men, the sperm functions – concentration, motility or morphology may be poor; or the DNA may be damaged. This could be attributed to advancing age or lifestyle disorders – smoking, drinking, obesity, stress etc. Computer Aided Semen Analysis (CASA) is a test performed to screen for male fertility problems. Treatments to improve sperm quality include suggested use of antioxidants such as zinc along with making lifestyle changes. Intracytoplasmic sperm injection [ICSI] is a technology used for fertilising an egg with a chosen quality sperm to help develop high quality embryos and correspondingly improve the implantation success rate per cycle. Donor sperm can also be considered as an option.

The Embryo: An embryo that contains a normal number of chromosomes i.e. 23 pairs of chromosomes in each cell, is called a ‘euploid’ embryo. An embryo that carries an abnormal number of chromosomes is ‘aneuploid’. Examples of aneuploid embryos include those with 18 sets or 21 sets of chromosomes, or maybe a single additional or missing chromosome resulting in a total of 47 or 45 chromosomes instead of the usual 46. There are high chances of the uterus rejecting an abnormal embryo resulting in an implantation failure. Pre-genetic Diagnosis (PGD) and Pre-genetic Screening (PGS) technologies can be used to identify healthiest embryos for implantation.

The Uterus: A successful implantation depends on the embryo quality as well as a receptive endometrial environment. The uterus may be affected by either structural, hormonal or immunological conditions which may be the reason behind the repeated implantation failures:

  • Fibroids,
  • Polyps,
  • Adenomyosis endometriosis,
  • Intrauterine adhesions,
  • Abnormal uterine shape,
  • Difficult cervix affecting embryo transfer,
  • Early rise in progesterone prior to egg collection in an IVF cycle,
  • Natural killer cells / immune system.

Treatment for all the above listed conditions is very much possible and can be opted for once the actual cause of RIF is identified.

In addition to the above, general maternal – paternal health concerns could also be a reason behind recurrent implantation failures. Lifestyle diseases – obesity, stress, excessive smoking or alcohol intake, improper work-life balance, unhealthy diet and physical inactivity are some common factors that both the partners need to take care of when planning to start a family.

Certain other maternal health factors affecting recurrent implantation failure include:

  • Systemic diseases such as diabetes,
  • Antiphospholipid syndrome i.e. autoimmune and blood clotting disorders,
  • An elevated level of Natural Killer cells (immune cells that are particularly prominent in the uterus around implantation) in either the blood or the uterus,
  • Thyroid dysfunction – both hyper and hypothyroidism,

Most importantly, STRESS – both physical and emotional, is a natural part of assisted reproductive treatments and its impact on IVF cycle success rate is difficult to measure. Hence it is important for the partners/individuals to do whatever will help put them in the best physical and emotional frame of mind during the course of the treatment – take regular counselling sessions, make lifestyle changes, surround themselves with loving and supporting family and friends, meditate – basically stay happy, healthy and positive.

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