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Undergoing IVF treatment and diagnosed as unexplained infertility. What could be the reason? Suggest suitable treatment?

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Answered by

Infertility Specialist
Practicing since : 2000
Answered : 3767 Questions
Dear Dr. Malpani,

We (XXXX-36, XXXX-33) live in the U.S. (Boulder, CO) and have been undergoing IVF treatment since XXXXXXX 2011 at Colorado Center for Reproductive Medicine (which is considered be one of the top fertility centers in the US based on their success rates).

So far we have performed four IVFs in the past 1.5 years, but haven’t been successful.We were supposed to be ideal candidates, but at this point diagnosed as unexplained infertility.

We would be happy to set up a telephone appointment with you too. Please let us know if that can be set up. We will appreciate if you can review our case and give us your opinion. Please let us know your consultation fees and we will make appropriate arrangements for payment.

Test results:

1. No male issues (good sperm count, motility, morphology, no Antisperm Antibody): all normal
2. No female issues (no uterine polyps, fibroids, Hysteroscopy clear, good hormone levels of FSH, LH, AMH, Estrogen, prolactin, TSH: 1.5, AFC: 14-17,
3. Beta integrin proteins present
4. Karyotyping on both of us-normal.
5. All communicable tests are normal (HIV, STD, Hep-A, Hep-B).
6. Tubes open, checked w/ HSG.
7. Antiphospholipid antibodies-normal

We have not yet performed the following tests (because our RE doesn’t think that they are necessary):
· Immune testing (e.g. NK Cells, Matching DQ Alpha, etc.)
· Blood Clotting tests (Thrombophilia)- But we have done APA which is normal
· No laparoscopy- So don’t know whether we have Endometriosis (according to our RE, this shouldn’t be an issue as we have beta integrin proteins)

However, some of the issues we have seen are:
· Irregular periods (we believe mainly due to tendency of taking stress/tension),
· Blood flow to uterus not perfect (seem to get affected w/ stress)
· Sub-clinical hypothyroidism (taking 25 mcg Levothyroxine 1/day)

Our IVF History:

1. IVF 1: Fresh Tx of 2 of Day 5 blastocysts (4AA, 4BA)-BFN
2. FET 1: 2 Day 5 Blasts (3BB, 3BB): Miscarried at week 7 (according to RE mostly due to abnormal embryos)

a. Blood flow to uterus normal, Lining ~10 mm

3. FET 2: 2 genetically normal day 5 blasts (4BB, 4BB) (they perform comprehensive chromosomal testing where all 23 pairs of chromosomes are tested)- BFN

a. Blood flow to uterus was significantly hampered (PI of >5 on both ovaries 5 days before ET), tried to correct it through vaginal Viagra from 5 days before ET till the day before the ET.
b. Lining ~8-8.5mm

4. FET 3: 2 genetically normal blasts (Day 6 5AA and Day 5 5AB)-Biochemical (Betas: 117, 143, 69)

a. Blood flow was somewhat hampered, used vaginal Viagra for about 2 weeks, stopped 5 days before ET.
b. Used estrogen estrace since 5 days before

5. Basically, I respond well to stimulations, produce high quality, genetically normal Day5 or Day 6 blasts. But end up either with no pregnancy at all, or miscarriage or biochemical pregnancies.

a. Avg. various parameters per cycle:

i. Eggs retrieved: 17-22,
ii. Fertilization: 11-17 embryos,
iii. Blastocysts Formation: 5-7
iv. Genetically Normal Embryos w/ CCS: 3-4

We would like to seek your opinion on the following questions:
1. What may be the reasons that are hampering our chances?

o We have failed IVFs w/ chromosomally normal Day 5 blastocysts.

2. What additional tests would you recommend we should perform? Are we missing any important parameters?-
3. Could potentially undiagnosed Endometriosis be causing this?-
4. Could the toxicity of vaginal Viagra might have led to implantation failure and miscarriage during our last 2 transfers when genetically normal blasts were transferred?-

a. 3rd transfer: Viagra was given till 1 day before ET- BFN
b. 4th transfer: Viagra was stopped 5 days before ET- BFP/chemical, Betas: 117, 143, 69
c. 2nd transfer: No Viagra, BFP, miscarried at 7th week (mostly due to abnormal embryos). This may indicate that uterus may seem to be working fine as long as blood flow is adequate.

5. Is there any specific Indian origin male or female issue that we may be overlooking?
6. What do you recommend we do for our next transfer?

a. We have 4-5, day 5 chromosomally normal blastocysts. We would like to do the ET soon.
b. Shall we do anything different?
7. We were advised to undergo genital TB test by an Indian doctor. Do you think that it would be necessary considering that my tubes are open, no findings on hysteroscopy, my linings are always good (between 9-10 mm) for embryo transfers, no history of pulmonary TB.

With best regards,

Posted Thu, 12 Sep 2013 in Infertility Problem
Answered by Dr. Mahesh Koregol 10 hours later
Brief Answer:
Hi XXXXXXX I understand your anxiety. Let me answer

Detailed Answer:

I understand your anxiety. Let me answer them one by one:

1) As far as I see your reports, everything seems to be good. If blastocysts are formed, it means good egg and sperm.

2) I dont see need for any other tests. as of now.

3) Undiagnosed small endometriosis would not have caused this problem. If there were big endometrioma in ovaries, it could have been seen in scan which is not the case. Hence dont worry about endometriosis.

4) Vaginal viagra was given to improve endometrial thickness. Its toxicity wont affect. But if the endometrial lining is more than 7 mm, you may opt for not using vigra.

5) Your failure has nothing to do with indian origin.

6) I suggest you undergo hysteroscopy to evaluate uterine cavity.Since already there was a pregnancy and miscarried at 7 weeks it is better to evaluate uterine cavity for polyp / fibroids by hysteroscopy.

7) There is nothing much that you can do other than testing endometrial biopsy for tuberculosis by PCR. Persistent thin endometrium in Indian women is sometimes due to past tuberculosis of genital tract especially in Indians. It is better to opt for PCR to check TB and proceed if negative.

Dr. Mahesh Koregol
IVF & Infertility Specialist
Above answer was peer-reviewed by
Follow-up: Undergoing IVF treatment and diagnosed as unexplained infertility. What could be the reason? Suggest suitable treatment? 3 hours later
Thank you Dr. Koregol for answering our queries.

Our follow up question:
XXXXXXX never had an issue with thin endometrium. She always had endometrium thickness of 9 mm to 10 mm before blastocysts tranfers. Viagra pill was prescribed for the restricted blood flow to the uterus and not for the endometrial lining issues. Also, her tubes are open on HSG. Do you still think that the genital TB could be present in her in spite of good lining, open tubes and could a cause for failure.

We also read that the TB-PCR gives a lot of false positive and is not a very reliable method for the diagnosis. Is that true? Is this the only diagnostic method to evaluate whether she has genital TB or not? Is there any other more reliable method?

We will appreciate your response.



Answered by Dr. Mahesh Koregol 3 hours later
Brief Answer:

Detailed Answer:

With such good endometrial thickness and earlier pregnancy ended in miscarriage, I believe tuberculosis may not be there. But it was adviced to rule out the possibility.

You are right there are false positive results. But it is the best method available as of now. No other methods are much reliable.

Dr. Mahesh Koregol
Above answer was peer-reviewed by
Follow-up: Undergoing IVF treatment and diagnosed as unexplained infertility. What could be the reason? Suggest suitable treatment? 33 minutes later
Thank you Dr. Koregol for your response.
Dr. Koregol,

Do you recommend any immune testing to test for NK cells activation and for any clotting issues (thrombophilia panel)? etc.?

Some doctors prescribe low dose steroids and blood thinners to overcome these issues. Do you recommend them too in case of such failures?

Answered by Dr. Mahesh Koregol 6 hours later
Brief Answer:
no role of testing for immunological profile

Detailed Answer:

We have to remember the fact that already you had a pregnancy but miscarried. Hence there is no role of testing for immunological profile or NK cells or even thrombophilia profile.

Rather than testing it is better to start low dose steroids and blood thinners like low dose aspirin and low molecular weight heparin empirically after next embryo transfer. It might help

Even though blastocysts were genetically tested, it is not possible to test all the possible genetic defects as still there are so many that are not tested. Hence probably miscarriage was due to some chromosomal problem i believe.


Above answer was peer-reviewed by
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