Physician-To-Physician Consult

Dear Colleague,

I saw today in my office a 41 year old healthy female, with primary infertility of one year duration, after failing in several COS+IUI cycles.
Her mechanical work-up was normal, and so was the semen analysis.
She has short cycles (24/3), normal BMI (20), and apparently a very low ovarian reserve:
Her basal FSH was 15.3 IU/L, AMH less than 0.3 ng/mL, and antral follicle count of 5.

I was debating whether she should start IVF or proceed directly to oocyte donation?
If IVF, how should I stimulate her? What would be the best stimulation protocol for her?

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Answer by Milton Leong

The combination of short cycles, raised FSH, borderline low AFC, and low AMH all suggest that this patient is nearing the end of her fertility life. Thus she should be offered IVF as soon as possible, especially if this couple wants a biological child of their own.

Since she is still cycling regularly, we can assume that at some time an oocyte cumulus complex is present, and our aim is to find this in the appropriate time, and collect the oocyte. Since she has a reasonable AFC, ovarian stimulation with FSH in the usual way (day 3) is possible.
The following ways of preparing the ovary can be done: - all involve using GnRHantagonists
1. FSH sc injection dosage 150U - 300U per day, and expect to have a few growing follicles, but which will have a viable egg
2. Consider trying Elonva (MSD) the long acting FSH because this drug gives a very high FSH immediately and reaches steady state in about 3 days
3. watch the follicles by ultrasound until they begin to grow - which indicate that they are functioning, then add FSH 150U per day when they are growing and leading follicle is about 8-10mm.
4. Start with clomiphene for 3-5 days, and then add FSH when follicles grow to 10mm or more.

3&4 will be easier for the patients, and cost less, and likely with the same or better results

In all three regimes, add antagonists appropriately, probably starting when leading follicle of 14mm or more.

Monitor with plasma estradiol and ultrasound as usual and more frequently, as older women tend not to have linear growth.
You will likely collect 3 eggs, have 2 embryos to replace. Based on endometrial thickness and sub-endometrial blood flow, you can decide if adjunct treatment is necessary.
Other adjunct treatments like testosterone patch, DHEA, coQ10, vitamin E, acupuncture etc can all be given to boost results in some, and to boost morale in general.
Should there be only one or two embryos, banking them is a very good decision especially when there is asynchrony or suboptimal endometrium as is often with older women.
PGS can be another adjunct treatment for consideration. Good luck

Dr Milton Leong.
The Womens Clinic Hong Kong
Adjunct Professor O+G McGill University

Answer by Matan Yemini

Medically egg donation is not just the best option but the only option
For long time we have treated Pt with high FSH who like to try first IVF and have been denied treatment by other centers
There is some low chance for Pt up to age 40
We have no take home baby for age 41 when FSH is above 10
Never the less some Pt will not go for egg donation unless try first IVF

Dr Matan Yemini
Diamond Institute for Infertility, NJ USA

Answer by Norbert Gleicher

In our program this patient would have a ca. 30% chance of clinical pregnancy. She suffers from premature ovarian aging (POA).
If you test her androgens you will find very low total (TT) and free testosterone (FT). We, therefore, would place her of DHEA 25mgTID x 6-8 weeks, until either her FT and/or her TT has reached the upper one-third of normal range for all ages (i.e., the level where this woman was at younger ages). Only at that point would we start stimulating her. Her stimulation would be a microdose agonist cycle with 450IU of FSH and 150IU of hMG daily. Since she suffers from POA, she is at significant risk that her POA is autoimmune in nature. We, therefore, would do a detailed search for autoimmune abnormalities. If this is her underlying problem, we would add to the cycle a treatment regiment of bASA, prednisone and lovenox/heparin. If her immune abnormalities are very pronounced, we would add IV-Ig. Good Luck!

Norbert Gleicher, MD, Medical Director and Chief Scientist, The CHR
President, Foundation for Reproductive Medicine, New York, NY

Answer by Qi Yu

Poor responder is one of the most difficult issues in the process of assistant reproductive medicine. The case had a basic FSH level over 15IU/L, which indicate a poor ovarian reserve. So there would be 3 methods for the case, but none of them could be perfect.

1. Try to increase the ovarian response:
1) DHEA for 3 months;
2) Growth hormone 4-6u every other day from day 2 of the period for 3-4 times for 3 months;
3) Some kind of herb medicine;
4) OC for 3 months.
Whether or not the above methods will be effective is not sure.

2. Do IVF directly.
1) Antagonist method;
2) Minor stimulation;
3) Nature cycle.

3. Oocyte donation, which means the women could not have the baby of her own.

Dr. Qi Yu
Department of obstetrics and gynecology, Peking Union Medical College Hospital
1# Shuaifuyuan, Dong Cheng District. Beijing 100730, P.R. China

Answer by Harry Siristatidis

The answer is very simple: there is very low chance of a take home baby.

Try mild (conventional or modified, as described above, with antagonists) or natural cycles protocols IVF, as soon as basal FSH and AFC permits it, supplemented by testosterone and/or LMWH and prednisolone for 2-3 cycles, preferably with a time interval from 2 to 3 months.

Good luck. 

Harry Siristatidis

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

Answer by Joaquín Llácer

FSH, AMH and AFC are predictors factors of ovarian response but the best test is to try to stimulate the ovary.

Probably a conventinal stimulation adding LH activity (rLH, hMG-HP or hCG) could be the first option. 

The use og Transdermal Testosterone seems advisable. Use of GH is very expensive and the action mechanism probably is not different from Testosterone.

The patient must understand that the prognosis is poor because the combination of POR and age, but I\'d try before considering egg donation. 


Joaquín Llácer. Instituto Bernabeu. Alicante. Spain.

[email protected]

Joaquin Llácer

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