Physician-To-Physician Consult

Dear Colleague,

I have a patient who is 31 years old. She was stimulated for her first IVF with hMG 150 IU per day for 7 days. The estradiol level reached 3400 pmol/l and the follicles reached 17 to 22 mm in diameter in both ovaries. Unfortunately, the endometrium remained 3-4 mm in thickness. Egg collection was done, 11 eggs collected, 8 fertilized, 5 blastocysts were developed and 2 replaced, 3 were cryopreserved. The patient did not conceive.

How would you recommend to proceed?

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Answer by Zeev Shoham

Based on our experience I would like to suggest doing an endometrial irritation during menstruation, using the pippele catheter and replace one blastocyst if the endomnetrium will reach 6-8 mm in diameter along with follicular development. i.e. to follow a natural cycle while doing a pippele during menstruation.

Zeev Shoham

Answer by Ariel Weissman

I would like to look at the patient's history and look for a reason (correctable?) for her thin lining. I would be more relieved if her thin lining is "primary" (no procedures or instrumentation were carried out in the past on her uterine cavity). If the patient was subjected to D&C or endomeritis in the past, I would start to worry... In any case, I would not proceed without a diagnostic hysteroscopy, which could be combined with pipelle biopsy as suggested above. I would than proceed to frozen embryo transfer during a natural cycle, and if there is insufficient lining build-up I would switch to estrogen replacement therapy, including transdermal and vaginal estrogen.

Ariel Weissman

Answer by Norbert Gleicher

I agree with need for a full work up to diagnose potential underlying causes. In the end, however, the treatment approach will, likely, remain the same.
I cannot respond in regards to endometrial irritation for lack of personal experience, though the literature appears to increasingly support such a response in cases of implantation failure.
I am, however, unclear whether such a response has been reported to help in cases of unresponsively thin endometrium. My suggestion would be to perform a mock cycle to see whether
the patient's endometrium can be expanded with routine treatments, such as increased estradiol dosages (transdermal, vaginal and oral) and Viagra (or beta-blockers; we use Atenolol). If she reaches 7mm,
I would give her the same treatment in a regular IVF cycle or FET cycle. If she does not reach 7mm thickness, I would attempt expanding her with an endometrial infusion Granulocyte Colony Stimulating Factor (G-CSF), as we reported initially in Fertility & Sterility and more recently in Human Reproduction in a larger case series of women with otherwise resistant endometrium.

Norbert Gleicher, MD

Answer by Ilan Tur-Kaspa

I addition to all of the above comments, I would monitor her natural cycle to evaluate her 'baseline' endometrial thickness. If she'll have a normal hysteroscopy and she'll have over 7-8 mm of endometrial thickness, ET may be performed without any other interventions. 

Prof Ilan Tur-Kaspa

Answer by Andre Hazout

It was not necessary to transfer two blastocysts in such endometrium. You could vitrify the embryos and make an assessment ; It depends on the history of the patient.An hysteroscopy is indicated to evaluate the endometrim status. If the cause is not iatrogenic, I agree with the proposed treatment (estrogen, viagra, G-CSF etc..)elsewhere, emphasizing the research of subclinical infection. Note also the role of melatonin on the endometrial growth. Unfortunately in our experience it is not easy to restore a normal endometrium with the best receptivity.Endometrium biopsy is not recommended if the endometrium is very thin and often not informative unless if you have the opportunity to perform a genomic profile

Answer by Harry Siristatidis

I agree with all the above. If it is <6mm, you freeze (vitrification is a simple good solution). Hysteroscopy is indicated in most of the cases to make a clearer judgment. You do not procced with endometrial injury, unless you have an indication of doing so - and thin endometrium is not an indication. Then you monitor 1 - I would say 2- natural cycles, to check if this is being repeated, or it was accidental. If it remains the same, you go for HRT/FRC, as mentioned above, with high rising dosages of oestrogens.

Harry Siristatidis

IVF Unit, Attikon University Hospital, Athens, 12642, Greece

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