Low Ovarian Reserve

Dear Professor Winston,

I am a 36 year old who has been trying to conceive with my 40 year old partner for one year. I have been diagnosed with low ovarian reserve. My AMH result was <0.6pmol/L, my antral follicle count was 3 on day 5 of my cycle. In the same month my endometrial thickness was 6.5mm on day 23. I had my progesterone tested on a different month and at day 21 it was 15nmol/L. I have a regular cycle, but most months have some spotting during the week before my period. Occasionally I have a small amount of spotting around the time ovulation should be occurring. Scans have shown that I have normal uterus and ovarian morphology and good blood flow in my uterine arteries. My LH, FSH and oestradiol levels have varied, with LH in the normal range (0.9, 1.8, 3.1), FSH normal or (I have been told, but don’t have the results) high (4.2, 5.5, 6.4) and oestradiol high (461pmol/L). My prolactin was in the normal range (294, 376), and thyroid function and other tests were all normal. I was told that my high oestrogen may be caused by my vegetarian diet that includes soya products, so I have tried to cut down on these and am also moving towards becoming vegan. I don’t smoke or drink alcohol or caffeine, and exercise regularly. I have in the last few years had borderline smears with a diagnosis of CIN1, and had a loop excision (also due to an ectropion) but my last smear in Feb 2013 was normal. My partner’s semen analysis has been normal twice. We were told by a private clinic in London when my tests came back that, as our chances of conceiving naturally were so low, we had no option but to have IVF. We went ahead and had a cycle straight away, which cost us (with all the preliminary tests) around £10,000. The protocol was high dose (450iu Gonal-F), we had only 2 follicles with good growth, one fertilised abnormally and the other was transferred as a grade 3 embryo, but failed to implant. We were told afterwards that this embryo divided more rapidly than they would have liked, so may have been abnormal. I have recently been to a different private clinic who specialise in natural/mild IVF and they have suggested a low dose (150iu Gonal-F) cycle with ICSI due to our previous failed fertilisation. I also have an upcoming appointment with the NHS, but so far the impression I have got from them is that they will not fund me as my chances of success with IVF are below 10% given my low reserve.

I have many questions, but my main question is whether in my situation, with low egg reserve, is it worth doing any further diagnostic testing before going straight into IVF, for example HyCoSy, or x-ray, or is there no point and no time to waste (as I have been told)? Also is IVF actually the right thing for me? Is it going to increase my chances enough to be worth it? Donor eggs have been mentioned on a number of occasions, but no guidance as to when we should stop trying with my eggs has been offered. Also, no one seems concerned about the spotting I’m experiencing, but I understand it could be indicative of an ovulation or tubal problem. I am also rather concerned about ICSI, the increased chances of abnormality and potential epigenetic effects – is this something you would suggest we steer clear of until we’re sure there is a problem with fertilisation, or again, do we not have the time to waste? I work in genetic diagnosis, so possibly have more idea than most of the potential abnormal outcomes and how the scientific process works. But even so I feel thoroughly confused, vulnerable and have no idea who to trust when it comes to IVF. I’m finding it very difficult to find independent, accurate advice and feel that we may have been rushed into our first round of IVF and sold treatments such as the endometrial scratch and intralipid infusion (at a cost of about £700) without proper explanation of whether they were really going to be beneficial for our situation (we felt we should throw everything at our attempt, but were left feeling a bit duped). I, perhaps blindly, trusted that by going to an expensive London clinic and speaking to experts in the field that we would be getting the best advice possible, but I really don’t know what to believe anymore. I attended the Progress Educational Trust’s Commercialisation of Life conference the other day and saw you speak, which helped confirm a lot of my fears about the IVF business, but also opened my eyes to the kind of questions I should be asking. Thank you so much for this service and your blog, it’s the first source of advice I have found that seems measured and sensible. I imagine you’re incredibly busy, so I really appreciate you finding the time to answer these questions. Best wishes, C

Dear C,

Even allowing for the fact that the AMH test is not nearly as accurate as is widely suggested, it does seem that your ovaries are not producing enough follicles and that you have a degree of ovarian failure. This is very much supported by your IVF response. However the FSH levels you send me are not high so I don’t know why you were told this – are you sure these are the right results? The spotting and the thin endometrium are also most likely to be associated with the falling ovarian function.

  1. The diet is, in my view, totally irrelevant. I just do not believe that any soya products could really affect oestrogen secretion to that extent – otherwise we would have a new contraceptive with minimal side effects, which is definitely not the case.
    2. HyCoSy is close to useless; all kinds of false positives and negatives are really quite common. There is no substitute for an HSG done properly.
    3. Have you had a laparoscopy to confirm you have not got any signs of pelvic inflammatory disease which could well reduce ovarian function?
    4. There is no serious evidence that the ‘scratch’ or ‘intralipid infusion’ has any place in treating patients with your history.
    5. Do not be ‘sold’ ICSI. This is an irrational suggestion and in my view this is evidence of a private clinic thrashing around because they haven’t got a clue what to do. I do not think they are necessarily being avaricious, but the net result is the same. Did they do a post-coital test (which costs a few quid at most) to see if your husband’s sperm were swimming around a day after sex, or has anybody recorded a failure of sperm attachment suggesting a molecular problem?

Personally, given what you have told me I would be inclined to avoid IVF totally – low or high dose stimulation. Statistically, your chances of getting pregnant are probably better trying naturally (with frequent unstressed, pleasurable sex) than with any form of assisted conception – providing your uterus is normal, your tubes are open and there is no evidence of pelvic inflammatory disease. Clinics seem to seldom tell patients this – I do not know why. But the number of patients in similar circumstances who conceive after giving up IVF is testament to the fact that IVF in this situation is not a very good choice for a large number of women.

Best wishes
Robert Winston