Should I have all those expensive tests?

Dear Professor Winston,

I am 35 years old and I have been trying to have a baby for 5 years now without success. I have had 4 attempts at IVF using my own eggs. However, due to my low AMH and poor ovarian reserve, I did not achieve a positive pregnancy test.My consultant decided that my best option would be to go down the egg donation route.
Following this advice, we have had 3 attempts at egg donation IVF at a clinic in Spain. Unfortunately, each of these 3 attempts have ended in biochemical pregnancies.
Please see below my Treatment Summary:

Pre-IVF treatment GP Blood Tests
11/08/2014
• Immune to German measles
• Do not suffer from anaemia
• Thyroid function is normal
• Baseline hormone tests are normal

01/10/2014
• Ovarian hormones are normal; in the month monitored, I had an ovulatory cycle

17/06/2015
• Cervical screening test was normal

NHS
30/12/2014
• Normal FSH and LH levels
• Immune to Rubella
• Normal prolactin and thyroid function

Semen analysis:
• High concentration
• Good rapid progression
• Isolated agglutination seen (request to repeat semen analysis)

17/03/2015
• Hysterosalpingogram showed normal uterine cavity and patent fallopian tubes
• Ultrasound scan was normal

Repeat Semen analysis:
• Normal count of 287 million/ml
• Motility 66%
• 5% normal forms with no agglutination reported

30/09/2015
IVF treatment cycle 1: paid by NHS
• High stimulation: 225 units of Menopur increased to 450 units
• 6 eggs collected, more follicles present but appeared to collapse during egg collection
• 3 eggs fertilised normally
• 2 embryos transferred on day 3 (1 x 5 cell, 1 x 3 cell)

16/11/2015:
AMH level = 10.4 pmol/l

Private Hospital
March 2016
IVF treatment cycle 2:
• Endometrial scratch
• Long down regulation of 450 units Menopur
• 9 eggs were collected, 4 fertilised normally (of the remaining 5 eggs: 3 were immature and 2 were mature but failed to fertilise)
• 2 embryos were transferred on day 3 (8 cell, grade 3)
• 13/04/2016 – negative pregnancy test

19/04/2016:
Prescribed Clomiphene (Clomid) 50mg to be taken once daily from Day 2 to Day 6 of my cycle for the next 3 cycles.

07/10/2016
IVF treatment cycle 3 (Short Protocol):
• Endometrial scratch
• Cetrotide protocol
• Combination of Bemfola 300 units with Menopur 150 units
• Cycle abandoned – singular follicle response (1 follicle of 10mm and 3 follicles of <10mm on right side, 1 follicle 23 x 20mm and 1 follicle <10mm on left side) • HCG trigger and timed intercourse • Pregnancy test – negative • AMH test requested 06/12/2016 AMH level = 2.1 pmol/l 12/01/2017 IVF treatment cycle 4 • Endometrial scratch • Testosterone gel 12.5mg daily • FLARE protocol 450 units of Menopur • 3 eggs were collected, 1 fertilised • Single embryo transfer (3 cell, grade 3) • Pregnancy test – negative • Advised best option is egg donation 31/03/2017 GP blood test: • Thyroid test – normal • Syphilis serology – treponemal antibody = Not detected • Serum TSH level – 2.41 mIU/L (0.30 – 4.50) • Serum free T4 level – 16.5 pmol/L (10.0 – 22.0)

25/04/2017: • HIV, Hepatitis B surface antigen, Hepatitis C antibody, HTLV antibody and syphilis antibody – all negative Spanish clinic Egg Donation Cycle 1: Mock cycle

21/08/2017: Ultrasound scan (Private Hospital): • Endometrium: 8.7mm full thickness and triple layer • Ovaries inactive Treatment cycle

13/09/2017: Ultrasound scan (Private Hospital): • Endometrium: 9.6 mm full thickness and triple layer • Ovaries inactive • 10 eggs retrieved from donor, 9 fertilised eggs after ICSI • 25/09/2017 – 1 embryo transfer, day 5 •

05/10/2017 – positive urine pregnancy test •

09/10/2017 – negative urine pregnancy test •

10/10/2017 – negative blood test Egg Donation Cycle 2: Treatment cycle (No mock cycle as followed on from previous cycle)

25/10/2017: Ultrasound scan (Private Hospital): • Endometrium: 8.6 mm full thickness and triple lines • No polyps or fibroids • No cysts or free fluid • Uterus normal • Ovaries inactive •

06/11/2017 – Frozen Embryo Transfer – 2 x Day 5 embryos thawed successfully and transferred. •

15/11/2017 – positive blood pregnancy test = 42 IU/L •

17/11/2017 – positive blood pregnancy test = 54 IU/L – Not doubled •

21/11/2017 – positive blood pregnancy test = 38.6 IU/L •

27/11/2017 – negative urine pregnancy test Egg Donation Cycle 3:

07/03/2018 • Hysteroscopy = uterine cavity is normal and tubal ostia were seen

27/04/2018 GP Blood tests: • Syphilis – negative Thyroid function test: • Serum TSH = 3.35 mIU/L (0.30 – 4.50) • Serum free T4 level = 18.2 pmol/L (10.0 – 22.0) • Hepatitis A, B and C – negative • HbA1C = 30 mmol/mol (20-42) • HIV negative 11/05/2018: Thyroid antibodies (Private Hospital): • Thyroglobulin antibodies = 11.1 IU/ml (0-115) • Thyroid Peroxidase Abs = 14.6 IU/ml (0-33)

29/06/2018 Ultrasound scan: • Uterus normal • No fibroid or polyps • Endometrium 10mm thickness and triple line • Ovaries inactive • No free fluid •

06/07/2018 – Frozen Embryo Transfer – 2 x Day 5 embryos thawed successfully and transferred. •

16/07/2018 – positive blood pregnancy test = 15.4 IU/L •

23/07/2018 – negative blood pregnancy test As the problem initially was thought to be my poor quality eggs, I thought we would be successful going down the egg donation route. Although I have achieved positive pregnancy tests, I keep suffering biochemical pregnancies. The 9 embryos produced using donor eggs (donor age – 23) and my husbands sperm progressed to Day 5 blastocysts. Therefore, they are thought to be high quality. I feel that I have exhausted every test possible and I am running out of options. My consultant has advised that my husband has chromosome karyotyping and FISH test. He has also suggested that I have a laparoscopy to check for hydrosalpinx, undiagnosed endometriosis, biopsy for infection and uterine abnormalities. These treatments are very expensive so I was wondering, based on my long treatment history, would you advise that I have these additional tests done prior to having further treatment? Is there any other treatment that you would suggest looking into? Your advice would be very much appreciated.

Dear I.,

Reading carefully through your notes and the multiple treatments you have had, the thing that stands out is that you were not fully investigated before these many and complex treatments were started.  I am not saying that the investigations would make a massive difference because clearly that is a big assumption. But nonetheless, your sad story which must have caused you great anxiety and expense, could be almost an object lesson for others.  Our profession has an obligation to make a diagnosis before, not after, treatment.   And hopefully, posting your important email on this website might persuade more couples to take more control of what what is being advised and is being being done for them.  Medical treatment without a diagnosis is mostly bad medicine. It is essential to make every attempt understand the underlying cause of the infertility before entering this demanding and complex treatment.  And I am sure anybody reading your very full account will understand the massive added distress of repeated failed early pregnancy.

I suppose, the other thing to say is that going overseas for treatments which are not widely available in Britain is often problematic. This is one reason why the regulatory body, the HFEA, should do more to facilitate the treatments you embarked on to make it less necessary for travel to other countries for treatments.  No matter how kind and competent the doctors may be there is often difficulty in communication with the nuances of language at a time of stress and anxiety.  Also there is always the question of the quality or competence of staff in clinics in some countries to which British patients tend to go.   This is of course, not a criticism of the country to which you went, but that gap in understanding is often an issue.

I agree with the advice your consultant has now given you, expensive or not.  It should have been done earlier, because your description is not a typical  description of ovarian failure and I wonder also, whether you are truly not capable of producing fertile eggs from time to time.  I do not know whether you have had a recent AMH and repeated FSH tests but to my mind this is really important because, before embarking on egg donation, you need every piece of evidence to confirm that you have no chance of conception without using donor eggs.  You can never be sure how the donor’s ovaries were stimulated, nor probably a really accurate detailed account of her reproductive history.  And unlike the tests you have now been recommended, what I am suggesting should be considered first is very cheap.

Why do I make this last point?  Experience has shown that very often in women with a poor response to ovarian stimulation at your age, natural conception does occur from time to time and in order to make every assessment of whether this is possible I think that all these tests could help you make better decisions – but I would first start with the cheap hormone tests to confirm where you stand.

I so much hope this useful to you

Best wishes,

Robert Winston