Advanced fertility procedures
A. Blastocyst culture:
Blastocyst culture means growing the embryo till blastocyst stage or till 5-6 days of embryo life. Embryos can be grown upto 2 days/ 3 days/ 4 days/ 5 days/ 6 days of life.
What are the stages of embryo development?
First eggs are fertilised by sperms / sperm is injected into an egg and this is considered as day 0. Then next day (Day 1) we check how many eggs have fertilised. Fertilisation is asses by observing 2 pronuclei (one female and one male pronuclei) in the egg. Then the embryo starts dividing. On day 3 it is known as a cleavage stage embryo and has 6 to 10 cells . later cell division becomes more rapid and the embryo starts becoming compacted starts forming an inner cavity. After 5 to 6 days of fertilisation embryo is said to be in a blastocyst stage.
How is blastocyst culture done?
Blastocyst culture is done only in advanced IVF labs under the guidance of expert embryologists. We require special media and conditions to make the embryo grow till a blastocyst stage.
How does a blastocyst look?
A blastocyst has an outer covering ( trophectoderm) and an inner group of cells (inner cell mass). Trophectoderm forms the future placenta and inner cell mass form the future fetus. Both are very important for implantation and causing a successful pregnancy. The outer covering of blastocyst secrete some substances which help in sticking to the uterine lining
Advantages of blastocyst culture:
Many studies have shown that blastocyst transfer (D5 embryo transfer) has a better success rate than any other embryos. Embryologists grade the blastocysts depending on the number of cells and their arrangement. By transferring a good quality blastocyst success rate can be drastically improved.
Disadvantages of blastocyst culture:
The main disadvantage is the number of embryos a couple has decreases. But these are anyways non viable embryos that is the reason they are unable to grow till blastocyst stage. In a way it helps us in selecting the embryos.
B. Laser assisted hatching
It’s a procedure in which a small hole is made in the embryo covering with the help of a laser. Generally embryo has a shell and it should hatch out of its shell and stick to the uterine lining for implantation to occur. In some cases this doesn’t happen and in such conditions laser assisted hatching can be very helpful
Previous implantation failure
For doing embryo biopsy
In this embryologist sends a strong light beam under a microscopr directed to one specific area over the trophectoderm/ embryo covering. This is to make a small hole in the embryo covering which can help in making the embryo hatch. There are other methods also of hatching like chemical , manual and piezoelectric methods. But this is the safest among all these methods.
It is a very safe procedure if done by an experienced and skilled embryologist. This is safer than chemical or manual methods.
PGT means pre implantation genetic testing. PGT A is a test done on embryos formed through IVF/ICSI to check for any chromosomal abnormalities. This test screens the embryos for any extra or missing chromosomes. These abnormal embryos are called aneuploid embryos and chromosomally normal embryos are called euploid embryos
This test can be done on 3 days old (cleavage stage) or on 5/6 days old embryos (blastocyst stage). First embryos are formed by IVF/ICSI. Later a hole is formed in the embryo’s covering with the help of a laser. Few cells are removed from the trophectoderm (which forms the future placenta) and sent for genetic testing. Normal embryos are then transferred into the uterus. Based on the results of PGT-A testing, PGT Treatment begins with a series of steps and decisions to select suitable embryos for uterus transfer.
For whom PGT Treatment is Recommended?
Advanced age ( > 38 years)
Repeated IVF failures
Family history of any genetic diseases
If parents have any chromosomal disorders/ genetic diseases
Any previous pregnancy with chromosomal abnormalities
Advantages of PGT Treatment
Increases pregnancy rates and implantation rates
Decreases the time to achieve pregnancy in IVF/ICSI
Increases chances of having a healthy baby
Disadvantages of PGT Treatment
Can increase cost of IVF treatment
Should be done by an experienced embryologist
Boon IVF’s PGT specialization: Boon IVF team has PGT specialists who have conducted 100s of PGT treatments. There are very few PGT specialists in Hyderabad and Boon IVF is proud to have one of the best PGT doctors and embryologists in Hyderabad who have successfully demonstrated one of the highest success rate. For more details, our team is happy to coach and give guidance to patients on pros/cons of PGT and help them in their decision making
D. ERA (Endometrial receptivity era)
ERA test determines whether the uterus of a woman is ready for embryo implantation. In this test few cells from the uterine lining are taken and sent for molecular analysis.
What is endometrial receptivity?
Endometrial receptivity is a period of time when the lining of the uterus is ready to accept an embryo. This time period is very important for a successful implantation.
Estrogen and progesterone hormones cause certain changes in the lining of the uterus and make it ready for implantation. In most of the women with regular menstrual cycles this window of implantation occurs between D19- D21 of their cycle. For a successful pregnancy to occur embryo must be in the uterus at this time. If the embryo comes too early or too late then implantation and pregnancy may not occur.
A mock transfer cycle will be performed. Serial ultrasounds will be done to see for the uterine lining and when the lining is good we start progesterone injections. We try to mimic the actual transfer cycle. After 6 days of starting progesterone injections we take a small piece from the uterus and sent it for molecular analysis. The report will come either as
Pre receptive: uterus is still not ready to accept the embryo and imlnatation is less likely to occur
Receptive : uterus is ready for the embryo and implantation is most likely yo occur
Post receptive: the lining has crossed the stage and is no longer ready to accept the embryo. Implantation is less likely to occur
Women with repeated IVF failures
This is not a part of routine fertility assessment and is not recommended for everyone. The value of ERA is still debated
It is an advanced procedure to select the healthiest and best sperm.
In india, 40 to 50% of infertility is due to male factor. Most of the men with male factor infertility have suboptimal sperm parameters. Assisted reproductive techniques are helping couples overcome infertility but not all attempts are successful. In ICSI we inject a good sperm into the egg. A very important step in assisted reproductive technologies is the sperm selection. Sperm quality can be effected by various things like smoking, alchohol consumption, obesity, advanced age, excessive heat exposure, varicocoele etc. microfluidics helps us in selecting the best sperm. Conventional sperm processing techniques like swim up and double density gradient cant differentiate sperms based on their DNA fragmentation.
What is microfluidics ?
It is a delicate device which helps in sperm sorting and selection. Its mainly used in men whose sperm has more DNA damage.
For whom microfluidics is advisable?
Men with high DNA fragmentation (DFI)
Couples with repeated miscarriages
Couples with repeated IVF failures
Men with advanced age
Men with some underlying medical conditions ( diabetes etc)
F. MACS (magnetic assorted cell sorting)
MACS is a technique to select healthy sperms and to deselect the sperms which are going to die .
What effect does a sperm with high DFI have on embryo development?
Sperms with high DNA damage have a negative effect on embryo development, low pregnancy rate and and higher miscarriage rates. Normal sperm processing techniques like swim up and double density gradient cant select sperms with least DNA damage. We need advanced techniques to select best sperms with low DNA damage (DFI).
Indications of MACS?
Men with high DNA fragmentation (DFI)
Couples with repeated miscarriages
Couples with repeated IVF failures
Men with advanced age
Men with abnormal sperm parameters
In MACS there is a magnetic column through which sperms are passed. Sperms aare mixed with magnetic nanoparticles and damaged sperms get attached to these magnetic particles. This sperm sample is put through the magnetic coulum and the damaged sperm are caught in the magnetic field and good healthy sperms are filtered out. These sperms are used for fertilisation process.
Benefits of MACS:
Higher fertilisation rates
Higher pregnancy rates
Less miscarriage rates
Better pregnancy outcomes
G. Frozen embryo transfer:
This is a procedure in which embryo transfer is performed with frozen embryos in a cycle other than the oocyte retrieval cycle.
A women gets comes down to the fertility center on D1 of her menstrual cycle. Few blood tests and a scan will be done to check for any cysts in her ovary and to check her endometrial lining. If everything is fine FET cycle will be started. Estrogen tablets will be prescribed which she has to take daily. Serial scans will be done to check her endometrial lining and when the lining is good progesterone injections will be started. Embryo transfer will be done 3 days or 5 days after the start of progesterone injection depending on the age of embryo. Frozen embryos will be thawed on the day of transfer. Blood test will be done 14 days after transfer and we will know whether pregnancy has occurred or not.
Who require FET?
People with a risk of ovarian hyperstimulation (PCOD/whose estrogen levels on the day of trigger are high/in whom we retrieve more number of eggs etc)
People in whom hormone levels are not so good on the day of trigger
Fibroid / adenomyosis ( we give some injections to decrease them and then we will plan for transfer of embryos)
In women who want to plan pregnancy at a later date
In cycles in which embryo biopsy is done ( as we need to wait for the results of the biopsy )
Is FET safe ? how long can we freeze the embryos?
We can freeze these embryos for any amount of time. The quality of embryos does not deteriote with time. The embryo survival rate is close to 90 to 95% . we can avoid the risks of OHSS and this is a relatively safe procedure with almost no side effects.
Which is better – frozen embryo transfer or fresh embryo transfer?
Many studies have shown that success rates with FET are better than fresh ET. Success rates of FET depends on age of the women, her underlying conditions and quality of the embryos. FET is a much safer procedure in patient with high risk of ovarian hyperstimulation (PCOS etc). only disadvantage is that the transfer cycle gets postponed in case of frozen embryo transfers whereas in fresh ET, transfer will be done in the same cycle as oocyte retrieval
H. IVM (In vitro maturation)
In IVM womens eggs are collected and matured outside the body, in the lab. Women are born with a fixed number of eggs and they are formed before birth. These eggs will be in a resting phase till a girl attains puberty. After menarche ( age when periods start ) these eggs will be activated and have the potential to fertilise and form an embryo. In a normal menstrual cycle woman develops one or two eggs naturally. In IVF we give injections to stimulate the ovaries to form many eggs and we retrieve these eggs. Not all eggs will be mature (ability to fertilise the sperm). Recent advancements have made it possible to mature these immature eggs and this process is called IVM.
A very minimal dose of injections will be given for a short duration of time. Eggs will be extracted early when the follicles are still small. These immature eggs will be matured in the lap under specific culture conditions . these eggs can be frozen or used for ICSI.
Why IVM and for whom?
Women with previous history of ovarian hyperstimulation (excessive increase in hormones)- some cases of PCOS will be at a higher risk of ovarian hyperstimulation which can be a life threatening condition. We can prevent this by using very minimal amount of drugs and performing IVM
In estrogen senstitive cancers (where giving IVF injections which increase estrogen hormones can be harmful to patients)
In patients who should not delay chemotherapy IVM can be done ( we retrieve the eggs immediately and decrease then time of stimulation)
Benefits of IVM
Low dose and minimal hormonal injections can be given
Short stimulation course
Cost of the treatment is less (as injections are less)
But pregnancy rates are also less so decision for IVM should be taken after weighing the risks and benefits
Do all patients require IVM?
The answer is no as pregnancy rates are lower with IVM when compared to traditional IVF. . only a few subset of patients mentioned above can benefit with IVM