Everything you need to know about Laser Assisted Hatching

 Saiprasad Gundeti, Chief Embryologist, Malpani Infertility Clinic Pvt. Ltd.

An embryo must break out or 'hatch' from its outer layer, known as the 'zona pellucida,' in order to attach to the uterine lining and implant in the uterus.

What exactly is Laser Assisted Hatching?

Prior to embryo transfer, a short laser beam is fired on the zona pellucida (Shell) of the embryo under a microscope to produce a tiny opening that allows the embryo to hatch. This increase the chances of Embryo Implantation.

When should Laser assisted Hatching be used?

1) Advanced Maternal Age (>37 years)

2) Patients with Several IVF Failures.

3) Embryos with thick shell (Zona Pellucida)

 

How is laser hatch done on Day 3 Embryos ?

Laser assisted hatching is usually done on day 3 Embryos (8-cell Stage)

Doing a Laser hatch on day 3 Embryos is relatively easier.

We find a gap between the cells where the laser can be fired safely away from the cells to make opening on the zona pellucida.

How is laser hatch done on Day 5 Embryos (Blastocysts) ?

Doing a laser hatch on day 5 Embryos (Blastocysts) can be tricky.

Since cavity is formed in blasotcyst, it expands and there is no gap between the zona pellucida and the outer cells (Trophectoderm)

The following are some effective ways of doing Laser assisted hatching on day 5 embryos.

In Fresh Embryo Transfer -

1) For a day 5 transfer at blastocyst stage, Laser beam is carefully fired on the outer part of the zona and a partial opening is made on the zona pellucida, without damaging the trophectoderm cells.  

2) The other effective way of doing laser hatch for day 5 Embryo transfer, is doing a laser hatch on day 3 and culturing the embryos till day 5.

The Embryos start hatching from the opening made on the zona pellucida before the transfer.

In Frozen Thawed Embryo Transfer (FET) -

If Blastocysts are artificially collapsed prior to Vitrification (Freezing) -

Blastocysts are artificially collapsed with the help of laser beam, to remove the water from the cavity.

This reduces the exposure time to cryoprotectants and thereby  increases survival rates post thaw

Because the laser beam is passed between the 2 trophectoderm cells to shrink the blastocyst, a tiny opening is made on zona pellucida. 

Hence there is no need to do laser hatch again prior to transfer in FET Cycle

 

If Blatocysts are not collapsed prior to Vitrification (Freezing) -

Although shrinking the blastocyst prior to vitrification gives better  post thaw surival, blastocysts can be vitrified without artificially shrinking them. In such cases -

1) Laser hatch can be done on the blasotcysts immediately after the thawing, when the cavity is less and there is gap between the zona pellucida and the outer layer of blastocyst (Trophectoderm) and then incubate (Culture)  the blastocyst for 2-3 hours.

2) If the blastocyst remains expanded post thawing, then a partial opening can be made prior to the Embryo transfer.

Laser assisted hatching is also used in Embryo Biopsy for Pre Implantation Genetic Testing  

A small opening is made on the zona pellucida to allow the biopsy pipette to aspirate few cells (5-6 cells for trophectoderm biopsy), which are placed in centrifuge tubes  and  sent to genetic Lab for testing

  

Need help getting pregnant? We provide a free second opinion for all infertility issues.

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How many IVF cycles will I need to do in order to get pregnant ?

 

Patients are better informed about IVF , and most understand that the pregnancy rate is not 100% in one cycle , which is why they may need 3 – 4 cycles in order to get pregnant . This is something they need to be mentally prepared for, so they have realistic expectations of the treatment , and can plan their time and money accordingly. Of course, the problem is that even though they understand this with their head, in their heart of hearts, every patient feels they will get pregnant in the cycle they are doing, otherwise no one would have the courage to even start the cycle.

If our IVF technology were perfect , we would have a 100% pregnancy rate and everyone would get pregnant in the first cycle itself , but we still haven't been able to achieve this goal because embryo implantation is a black box area , and we are not able to control what happens to the embryo once we transfer it back inside the uterus . This is because many embryos have genetic effects , which it's not possible for us to screen for . PGS does not help.

Since we can't predict whether the embryo will implant or not , you have to be mentally prepared for failure, so you don’t lose hope and give up. It’s important to learn from the failure, and continue trying , because over multiple cycles, your chances of getting pregnant will keep on increasing .

The reason young patients with good ovarian reserve need fewer cycles to get pregnant is because they usually grow lots of eggs , and generate multiple top quality blastocysts. Many will get pregnant in the first IVF cycle itself , simply because their embryos are much more likely to implant , because they are more likely to be genetically normal.

For these patients , the success rate is about 45% in one cycle , when we transfer a single top quality blastocyst, and over 3 cycles the cumulative pregnancy rate is better than 80%. The problem is that it's impossible to predict for an individual patient when they are going to get pregnant . We still don't know why a patient didn’t get pregnant in the first cycle , but got pregnant in her second cycle, even though top quality blastocysts were transferred in both the cycles.

Because we can freeze and store the extra embryos, the cost and stress in a second cycle is much less , because transferring frozen embryos after thawing them is a much simpler process, which doesn’t need injections, and usually only requires just 2-3 visits to the clinic . In fact, the scans can be done locally, so the patient can come to the clinic directly for the transfer.

However, for older women, or those who are poor ovarian responders, we may have to do multiple fresh cycles in order to generate enough embryos , which we can freeze and pool, and then transfer these embryos , one at a time , in order to maximize the patient’s chances of getting pregnant .

These are complex decisions which need to be made in partnership with the patient , which is why doctors need to be upfront , open and transparent. They need to explain the pros and cons so that patients have realistic expectations , and don't get fed up and frustrated just because one cycle fails.
Second cycles are much easier because the patient knows exactly what to expect , and this makes the journey a little easier , but the uncertainty and the two week waiting period ( 2 ww) never get easy , no matter how many cycles you do .

 This is why you need to remember that an IVF cycle is not just a treatment cycle , but also provides invaluable diagnostic and prognostic information , and we need to use this intelligently, so you can optimise your chances of completing your family.

If you want a free second opinion, please email me !

We look forward to helping you to have a baby !

 

IVF’s dirty little secret - the commonest reason for poor quality embryos is a poor quality IVF clinic

 

IVF’s dirty little secret - the commonest reason for poor quality embryos is a poor quality IVF clinic

The chances of getting pregnant in an IVF cycle are directly proportionate to the quality of the embryos created . If the embryo quality is poor, the chances of getting pregnant are going to be poor as well .

Now, the quality of the embryos created in the IVF clinic is a variable that is highly dependent on the skill, experience and expertise of the IVF doctors and embryologists, who need to work together as a team.

However, most IVF patients are completely clueless about the quality of their embryos. A major reason for this is many IVF clinics will hide this fact from their patients , by refusing to share embryo photographs , as a result of which patients are completely in the dark about this key variable. Doctors will causally tell all patients that their embryos are "top quality" – but will not provide any visual documentation to prove this.

To add insult to injury , when the cycle fails , and the patient demands to know the reason for the failure , they then tell the patient the cycle failed because the embryo quality was poor , and that the reason the quality was poor was because the patient’s eggs were bad , or the sperms were bad. They will cook up some flimsy pretext , which basically boils down to some variant of victim blaming. To make matters even worse,  they will then advice the patient to use donor eggs or donor sperm or donor embryos, or surrogacy in their next attempt in order to achieve a pregnancy.

However , the truth is that the reason for the poor quality of the embryos was that the IVF clinic was of poor quality . This is because the doctor who runs the clinic is inexperienced and doesn't have enough expertise or training. By attending a one week workshop , he calls himself an IVF specialist and starts experimenting on poor unsuspecting patients.

A big problem is that medical colleges do not provide any training in IVF,  as a result of which while most MD gynecologists may know a lot about the theory of IVF , they have no practical experience at all in dealing with IVF patients . They end up using their patients as guinea pigs , and their success rates are very poor during their learning process.

What's even worse is that many of these so-called IVF specialist are actually "part-time " IVF specialist. They are gynecologists, who continue doing anything and  everything , including caesarean sections, hysterectomies, and laparoscopies . Actually, IVF is a full-time job , and should only be done by a full-time IVF specialist who does nothing else , as is true all across the world.

Because they don't know enough about IVF , they try to import this IVF expertise, by doing what is called " batch IVF " , and hiring travelling IVF specialists and embryologists to carry out the procedures on their patients once every month or so. This may be very profitable for them, but it obviously means that the quality of care the patients receive suffers significantly.

Also , many IVF clinics will try to increase their revenue by appointing " consultant gynecologists " who will then use their facility in order to do IVF for their patients . The care of the patient gets compromised, because these gynecologists don't know enough about what's happening in the lab , and the poor patient gets trapped .

These very same patients who were told to use donor eggs by these bad IVF clinics then go on to generate very good quality embryos when they go to a good IVF clinic ! This clearly proves that the problem was not the quality of their eggs , but the quality of medical care they received.

Sadly most patients only learn the difference between a good IVF Clinic and a bad IVF clinic when their first IVF cycle fails, which is when they start doing their homework. However , this is an extremely expensive lesson , and because they have wasted so much time , money and energy , they don't have any confidence left in any IVF doctor , and will often refuse to try doing another cycle in a better clinic, as a result of which they fritter away their chance of having a baby.

 

How IVF can help patients with poor ovarian reserve to have a baby

 

Patients with poor ovarian reserve are difficult patients to treat for IVF specialists, and the success rate is usually poor. This is because IVF pregnancy rates depend on the quality of the embryos we  transfer, which in turn depends on egg quality.

Because they are poor ovarian  responders ,  the quality and quantity of embryos we are able to generate  for these patients is usually poor. This is why it’s quite challenging to help these women have a baby . You need to understand what your treatment options are , so you can follow this in an organised systematic fashion.

For patients who have had a poor ovarian response in an earlier IVF cycle , the first option is to increase the dose of injections used for super ovulation . It’s impossible to predict whether this will improve ovarian response, but it gives you peace of mind knowing you have explored all the possible options. For these patients, we usually treat them with Vitamin D and DHEA prior to starting the IVF cycle, because this can help to improve their ovarian reserve. Additional supplements such as growth hormone don’t have any beneficial effect , which is why we don't use these .

If the response to the increased dose of super ovulation hormones doesn't help , then our next step is to a mini stimulation protocol . This may sound paradoxical. After all, if a large dose of hormones didn’t work, then how will a smaller dose help ? The hypothesis is that if even using a large dose of hormones doesn't allow us to recruit a large number of mature eggs , then we might as well settle for recruiting a small number of mature eggs by using a lower dose of injections. Surprisingly , the response to this lower dose can be quite good in some patients , so this is a low risk low cost approach that is well worth trying. We will go ahead even if there is one single follicle in these patients, because each of these eggs is worth its weight in gold, and we need to maximize their chances of getting pregnant.

The aim of all these protocols is to get enough eggs so that we can generate enough embryos to give patients a good chance of having a baby. We pool these embryos in 3-4 sequential IVF cycles, and don't transfer any of them. Our goal is to store at least 3- 4 top quality frozen blastocysts before we start transferring them. Ovarian reserve keeps on declining as you get older , while your frozen embryos will remain as good as new , no matter when we use them.

It's true that this particular treatment plan takes quite a lot of time and can be quite expensive. This is why these challenging patients need to have realistic expectations of what IVF technology can offer them so that they have peace of mind they did their best in their quest for a baby.

If everything fails , then Plan B is to use donor eggs . This has a much higher success rate, and it’s easier to accept this option when you know that you have tried everything possible to get pregnant with your own eggs , but everything you tried hasn't worked.

Send me your medical details by filling in the free second opinion form  at https://www.drmalpani.com/free-second-opinion and I'll be happy to help you to have a baby !

 

Treating PCOS in infertile women

 

PCOD (Polycystic Ovarian Disease, PCOS or Polycystic Ovarian Syndrome) is one of the commoner causes of infertility in young women. The problem is there is a lot of confusion about this disease , because everyone seems to make this diagnosis at the drop of a hat – the nutritionist , the beautician , the neighbourhood aunt  , the sonographer, and the GP.

This is why infertile women with PCOD often end up getting poor quality treatment

Step number one is first deciding what your priority is . Do you just want to regularise your periods ( if your periods are irregular )? Or do you want to have a baby now ?

If you just want to get regular your periods , then all you need to take are inexpensive birth control pills, and these are very effective and efficient, and will ensure you will get regular periods as long as you take them regularly.

However, if you want to have a baby , your treatment options are very different – and birth control pills will not help !

The first line of treatment is lifestyle changes , especially for those who are overweight. Losing weight helps, but this is easier said than done, and will not work for all patients. 

The next step is medical therapy using medicines such as metformin and myoinositol to improve the abnormal insulin resistance which is so common in women . If this doesn’t work , then the next step is ovulation Induction with medicines such as clomiphene and letrozole. This may require follicle monitoring as well , to document that you are ovulating after taking these, as the dose varies from patient to patient.

If these simple treatment options do not work , then you might have to consider treatment by an infertility specialist . The simplest treatment option is IUI ; and if this fails , then the next step would be IVF . The success rates are a good clinic are excellent , but you should also remember that treating patients with PCO can be quite challenging , because when they don't grow eggs they don't grow any at all , but when they grow eggs , they often end up growing too many . This means you have an increase risk of multiple pregnancy when doing IUI , and an increased risk of ovarian hyperstimulation syndrome ( OHSS) when doing IVF , so that finding a good IVF clinic is extremely important

Another very effective treatment option for patients with PCOD is laparoscopic ovarian drilling ( a newer option is vaginal ultrasound guided ovarian cauterization) , to ablate the increased ovarian stroma which disrupts the hormonal balance by producing too much androgen.

This is specially useful for young women who have large ovaries , with increased ovarian volume , as well as increased stroma because we can then surgically correct the underlying problem . This means that your hormonal profile will go back to normal, and you can get pregnant without any further medical intervention ( provided your husband’s semen analysis is normal, and your fallopian tubes are open).

If you have more questions, please email me at [email protected] 

How to make sure your embryo transfer isn't difficult - the IVF patient's guide to easy ETs

Embryo transfer is the final medical procedure in an IVF cycle , and normally this is very straight forward , because all it involves is transferring embryos back into your uterus using a flexible , soft sterile plastic catheter called the embryo transfer catheter, which the doctor which the doctor negotiates under ultrasound guidance , through your cervix into your uterus.

However in some patients , doctors will have technical difficulties in positioning the catheter into the uterus . This is because the cervix was not designed to allow doctors to insert plastic tubes through them, as a result of which the procedure becomes challenging.

The cervical canal is not a straight passage, and in some women it becomes narrow - a condition which is called cervical stenosis , as a result of which the doctor will not be able to pass the soft ET catheter into the uterus without causing bleeding and trauma.

Doctors want to avoid a difficult transfer , because the trauma and bleeding this induces can cause uterine contractions , which will cause the embryo to get expelled , and result in a failed IVF cycle. 

Fortunately , we do have strategies to deal with this uncommon problem .

This is why many clinics do a mock transfer ( dummy transfer ) prior to the actual embryo transfer , so we can map the cervical canal and make sure the catheter goes through easily . In case, there is technical difficulty , we are prepared, and can use more rigid embryo transfer catheter sets , which make it possible for us to negotiate the stenosis, and deposit the embryo safely inside the your uterine cavity . We obviously don't want to be experimenting with catheters during the actual transfer itself !

In some patients , we need to do the embryo transfer under general anaesthesia , so that you are relax , and don’t have any pain. This is safe, but is needed in only a small minority of patients.

Rarely, we may need to do a hysteroscopy , if the transfer is persistently difficult, in order to check the cervical canal, and dilate it .

If this doesn’t work, then we may need to bypass the cervix completely, and deposit the embryos directly inside the uterine cavity , by using a special Towako transmyometrial embryo transfer catheter set , but the pregnancy rates with this are poor . 

If your IVF cycle has failed because the embryo transfer was difficult , and you need more help, please email me at [email protected]

The flipped consultation model can help you talk to your doctor !

 

One of the reasons a medical consultation can be very frustrating for both doctors and patients is that patients get brain freeze when talking to doctors , as a result of which they sometimes distort the facts or jumble them up or don't provide them in the right chronological order or forget to provide the right information , as a result of which the doctor cannot provide the right medical care because he cannot make the right diagnosis .

This is where the flipped consultation model can be so useful .

This is modeled after the flipped classroom model pioneered by the Khan Academy , where the students study the subject before going to class , so they are better prepared, and can use the teacher and their peers as educational resources to clear the points which they cannot figure out for themselves.

Similarly , in a flipped consultation model , patients do their homework before going to the doctor , prior to the consultation . They first write all their questions and doubts  down , and try answering themselves using all the free high quality medical resources available online from reliable websites such as those from the NIH, the NHS, Mayo Clinic, Harvard Medical School. www.drmalpani.com is very useful for patients who want to learn more about IVF.

Because you can do this on your own time , you can repeat the process by exploring multiple websites as well as the videos they create, so you will be able to understand exactly what is happening . These sites are patient-friendly because they are written in plain English , which means they are easy to understand .

This means that when you talk to your doctor , you will not get intimidated by the complex medical jargon which he throws at you during the consultation , in order to show you how expert he is. Also, because you have enough background information , you will be able to focus on your areas of doubt , which he will then be able to clarify , because he understands what your specific concerns are. This is a far better use both of your time as well as his.

While it's true that some old fashioned paternalistic doctors will take offense when Google Positive patients try to find out information for themselves , remember that good doctors respect well informed patients , and are happy to treat you as a partner in your quest for the right medical treatment , so that you can get better sooner. After all, you are both on the same side – yours !

If you need more information about IVF, please email me at [email protected]