Blastocyst transfer may help in repeated IVF failure cases

Recurrent implantation failure may identified after three failed IVF cycles or after transfer of 10 high grade embryos. There are many different factors which may contribute for this recurrent IVF failure, such as parental chromosomal translocations, abnormal uterine anatomy , hydrosalpinx, or inadequate  culture conditions or embryo transfer techniques.

Failure may be due to factors with the “Seed,Soil or the Cultivator”

Some studies have suggested that local injury of the endometrium by means of a catheter or hysteroscopy can induce an inflammatory response that may facilitate the preparation for implantation.

Artificial rupture of the covering of the embryo ( Zona pellucida) may improve implantation: Assisted Hatching, but is still not proved.

Pre-implantation genetic screening of the embryos is now a day used to get and select best embryos. But this strategy did not show any improvement in patient outcome  and did not show any significant difference on clinical pregnancy rates.

A few studies have reported that congenital and acquired prothromotic conditions are more prevalent in women with recurrent implantation failure. Therefore use of low molecular weight heparin (LMWH) and mini dosage of aspirin on patients with thrombophilia and recurrent implantation failure has been discussed, but large studies are required to prove them .

Finally, another possible strategy is to extend embryo culture to blastocyst stage, aiming to improve embryo selection and uterine receptivity

what is my ovarian status, asks one lady after two IVF failure

Mostly , IVF fails due to ” either defect in soil or the seed”, It is very difficult to accept for a couple when we say , that your embryos are not good and we cancel the embryo transfer.

The problem may be in Sperms or in Eggs. But most of the time , if sperm count is good , the eggs are responsible. ( here I should say that, we might also be responsible if our lab conditions are not appropriate, but at our center, we usually do quality control every day, and moreover, if there are two or three cases in one day, and others are appropriate, then we might feel, that we are not at fault).

Most of the time , couple asks a question: What went wrong, why my test is negative, Even they might ask , who is responsible for this failure?

We always do a egg quality  and egg number estimation before commencing the treatment, esp, in little older females.

It is done by Day 2 , transvaginal sonography and a blood test called AMH, that i anti mullerian hormone. It can be done in any day of the menstrual cycle

Role of emotional stress in fertility treatment

I see my patients (not patients, as they are healthy couple,but not able to reproduce) come for infertility treatment, and most of them are for IVF. They tried for a  long, naturally or with various treatments but feel helpless, as they couldn’t achieve it. So I can place them in psychologically stressed and partly frustrated.

“Rene Frydman and Alice Domar have emphasized the role of emotional stress( the stress of infertility has been compared to a diagnosis of cancer or infection with human immunodeficiency virus) in reducing oocyte competence.

Any stress, like ” Fight,Flight, Fright” generates a response, that mobilizes blood flow to the heart, muscles, and brain at the expense of ” inessential” organs such as ovary.  Frydman’s group in Paris showed in a landmark study of natural cycle IVF that the quality of blood flow to the mature follicle was strongly related to pregnancy outcome.They also refer to  another landmark study showing that an increased vascular response to stress predicts a reduced IVF pregnancy rate

Thus the patient has to be counseled to reduce the amount of stress during IVF treatment. Because it is our opinion too that, even we get good eggs and even we get good blastocyst, the implantation fails. It may be due to poor quality or poor energy(? mitochondrial energy) of the maternal oocyte.” ( Fert-Ster,page 545,Vol 105,No3/March 2016)

Extreme stress is a major contributor to the poor embryo quality and failed IVF.

Many female partners, in my center, seeking IVF treatment, are under too much stress . When I ask them for the reason, apart from infertility, few of them disclose that , they have a fear of left out by male partner and his family, because she is infertile and if this expensive treatment fails, they might be discarded by the family ( may not be an actual truth, but the guilt of being infertile breaks them)

Fear of loosing hard earned money, if treatment fails, is one of the major contributor of stress, in a self funding situation.

And top of that, when one IVF cycle fails, and they decide to go for second cycle, there is an added stress of previous failure.

I always try to communicate with the female partner and try to make her comfortable. I always tell them, when you are under my treatment, then we are friends, there is no doctor-patient relationship, we have to be informal in talking, and I am always available with you,any time you need any answer. It makes the situation little less stressful ( I suppose). I can not behave like or become a God, but we together can bang the door of “Him”, so that it may open the door of opportunity. If we don’t bang it with fullest effort, it will never open. To get a pregnancy, is our joint goal,  and with you guys, I am too very much fond of success.

I always ask them to do “meditation” ( a mind-body program). Sometimes I teach them, how to do it. It helps to release stress to a large extent.

I tell my patients, that while doing your treatment,I am under stress too ,  Because it is a great responsibility to give best from my side. I don’t know whether my treatment will be successful or not, but I have to overcome this stress and do my best, rest depends on “Almighty”. It is our philosophy, ” You do you best Karma, and for the result, leave it to the Almighty”. It is like a war. You always fight it to win it.

People have seen that: Even the Best Euploid embryo , diagnosed by Pre-implantation Genetic Screening , fails to implant in good endometrium. (Fert-Ster page 545,Vol 105,No3/March 2016)


Incubators in IVF laboratory

Triple gas incubators are usually of three types

  1. It is a bench top warmer and maintains the temperature and you have to feed it with triple gas mix, Mostly 90% N2, 5/6%CO2 and balance air. Here you are dependent on the manufacturer of the triple gas mix, and if it is not supplied properly then you are stuck and there is no incubator in your lab. Secondly, if you want to keep a particular pH in any sequential step, then you can not change the concentration of CO2 at your will or you have to order the separate gas mix. I find it very cumbersome and don’t rely on premix.
  2. Bench top system with inbuilt facility of mixing gas at our will, here we need pure CO2 and N2 feed. It is easy to obtain these cylinders. Here we can fix the CO2 concentration according our pH requirement of the sequential step. We use MIRI multichamber , its performance is good and gas consumption is very less. Fast recovery and we can dedicate each chamber for each patients without disturbing the other. There are other brands too in the market. They are definitely better than simple warmers.
  3. Box type triple gas incubators: These incubators are also with systems of gas mixing at our will. These systems are age old trusted partners of laboratory. Smaller the capacity of incubator, better is recovery and lesser is the consumption of gas. It is better to have a few small box type triple gas incubators , than having a single large incubator ( to accommodate many patients, they consume definitely large amount of gas, esp nitrogen) . We use ASTEC small box type triple gas incubators.

Our policy is : It is important to have a particular pH at different steps, rather believing the CO2 concentration shown on display. We keep CO2 according to the pH requirement, which you can not do with simple warmers.

Repeat Egg retrieval in same patient of Poly cystic ovarian disease

Here is a patient of 5 yrs of childlessness, she is a case of polycystic ovarian disorder. she came to us for IVF. We started her stimulation with Gonadotropins long with GnRh antagonist, Cetrorelix.

On maturation of the eggs may be on 9th day of cycle, we give the injection GnRh agonist, Busarlin, for the final maturation of the eggs, at 12.30 in night.

We did oocyte retrieval after 36 hours. But to our surprise, we found no eggs from the left ovary. We stopped the procedure, and we applied injection HCG 10,000 on same night again. We did repeat egg retrieval after 36 hours from the other ovary.

We retrieved 7 eggs. 4 were mature and at MII stage. ICSI procedure done on them.

On day 5 of embryo culture, we got one good blastocyst. Embryo transfer was uneventful. After 14 days we found the lady is pregnant.


IVF in previous ectopic cases ( pregnancy in Fallopian tube)

I saw lot of patients with secondary infertility who had ectopic pregnancy after their marriage.

It shows that :

1. They are fertile .

2. The sperms and eggs are usually of good quality.

3. The fertilization site , that  is fallopian tube is at fault.  The tube is patent, ,it allows sperm to go to the egg ,that is waiting at the outer portion of the fallopian tube. The sperm fertilizes the egg, but when the tube pushes the fertilized egg to the uterus , it gets trapped in the tube. It happens because the internal surface of the tube is not smooth. The uterus grows with the growing embryo , but tube can not, so it cracks and the patients land into the severe internal bleeding ( if not seen earlier part of pregnancy). Usually she gets operated and the tube with the pregnancy is removed. Now the lady is with only one tube left.

4. Now she tries for another pregnancy, but couldn’t achieve it. Why? ,as she is fertile, her periods are regular, ,she produces eggs in every month, and staying with her husband, but without pregnancy. This happens because : She had a pregnancy ( ectopic) with the better tube she had ( and it is removed, as she had ectopic). The tube left is usually inferior compared to the tube that is removed, Otherwise she could have a normal pregnancy with this remaining tube.

5. Now the treatment starts , and a Hysteros Salpingo graphy ( HSG) / laparoscopy is done to see the remaining tube , and report comes : patent tubes. Now she is confused . If the remaining tube is patent, then she should have  a natural pregnancy. On that quest : She undergoes lots of useless treatments, like multiple Intra-uterine inseminations (IUI). If her remaining tube is not good , then what ever you do ( with putting sperm in her uterus,IUI) fertilization does not happen.

6. This is because : Tube has to do three functions: a. give passage to sperms and eggs, b. Give nutrition to the fertilized eggs, c. Propel the fertilized egg( embryo) to the uterine cavity. Fault in any of the three function will hamper pregnancy in uterine cavity.

7. So the treatment is not putting sperms in uerine cavity (IUI) , as IUI has not created her earlier ectopic, The treatment is Fertilization. If it is not happening in tube ( in-vivo) , then she should have fertilization,In-vitro ,that is IVF

8. I see many patients with previous ectopic , who waste their time and money in these useless treatments. You can earn money but you can not recover the age. Age makes the eggs poor, and when they come late , the chances of IVF gets poorer. They are increasing their problems and reducing the chances of getting pregnancy because of their own ( ? treating physician’s) ignorance.

9. If they come early for IVF , the chances of success will be more as compared to primary infertility patients ( who never has pregnancy).

10. In India , the tubes are damaged due to Tuberculosis infection(?). some times this inffection damages the uterine lining also ( endometrium).

11. So more delay in getting IVF; May create problem in both ” Seed and the Soil”

Induction of Ovulation during IUI and IVF

In this issue:

1. Monitoring in Induction of Ovulation during IUI and IVF
2. Triplet ,after two blastocyst transfer, (Monozygotic twinning of one blastocyst)—Case report.
3. Training in IVF and Embryology

Continue reading “Induction of Ovulation during IUI and IVF”