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Rapid Responses: Rapid Responses published:
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Treating unexplained fertility
- Gary M Doherty (15 August 2008)
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Dissapointment
- Mark A Nettleton (16 August 2008)
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Nutritional factors in unexplained infertility
- Dr John A A Nichols, Professor Margaret P Rayman, Dr Andrew Taylor (4 September 2008)
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Gary M Doherty, SpR in Paediatric Respiratory Medicine Great Ormond Street Hospital for Children NHS Trust. London. WC1N 3JH
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I am unfortunately at one of those junctures in my career when I look more often at the back of the BMJ for jobs than at the front for inspiration. Not so this week. On the front cover, the headline ‘Treating unexplained fertility’ echoed the whispered, illicit conversations some of my colleagues have engaged in. These conversations occasionally follow examples of parental fecklessness, neglect or just plain cruelty. At times like these, the treatment of unexplained fertility has flitted across all our minds. Our ethical and professional values usually quickly reassert themselves and we realize that such treatment is not compatible with human rights. Had the BMJ grasped this nettle? No, although I am sure the heart rates of many medical correspondents for the national newspapers quickened slightly in the hope that it had, before they recognised the typographic error with 'fertility' replacing 'infertility'. Thank you, nonetheless, for raising a smile, and apologies to the authors of ‘Treatment for unexplained infertility’ that I got no further than the headline. Competing interests: None declared |
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Mark A Nettleton, General Practitioner Bridge Road Surgery NR32 3LJ
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Whilst the article on treatement of unexplained infertility is most satisfactory and a welcome information source,my dissapointment stems from the promise on the cover of this weeks BMJ. "Treating unexplained fertility" In my practice helping patients explain their often immaculate or at least "odds against" conception is a far more challenging clinical connundrum. This typographical error by the BMJ has put a smile on my face -thankyou ! Competing interests: None declared |
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Dr John A A Nichols, GP Researcher University of Surrey, Professor Margaret P Rayman, Dr Andrew Taylor
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We were interested in the commentary on the paper by El-Toukhy and Khalaf on the paper by Bhattacharya et al (1) in the same edition of BMJ, which showed very little benefit from either clomifene or IUI. This does not surprise us as we have been researching this area. Although you have cited cervical, uterine, ovulatory, peritoneal, immunological, or fertilisation defects as possible explanations for unexplained infertility, there is no mention of the factors we have been researching. Trace element deficiencies have long been recognised as causing infertility in veterinary practice (2) and oxidative stress has been suggested as a cause of blighted ovum (3) . Oxidative stress has been shown to cause very early pregnancy loss (4) and antioxidant minerals and vitamins have been shown to improve the outcome of pregnancy. For instance, in a randomised controlled trial in 60 women at risk of preeclampsia, Rumiris et al showed that a mineral and vitamin combination (Vitamins A 300 mg, B6 2.2 mg, B12 2.2 g, C 200 mg, E 267 mg, folic acid 400 g, N-acetyl cysteine 200 mg, copper 2 mg, zinc 15 mg, manganese 0.5 mg, iron 30 mg, calcium 800 mg and selenium 200 g) reduced very early pregnancy loss by 29% compared to supplementation with folic acid 400 µg and iron 30 mg daily (n=31/29) in patients at risk of preeclampsia (5). A small survey (n=87) on nutritional status and failed IVF has shown an associated with higher levels of the anti-nutrients cadmium and lead and lower levels of zinc and selenium (6). A beneficial effect from over-the-counter antioxidant multivitamins on the success rate for IVF might be expected: one research team found that measurements of antioxidant status of follicular fluid were improved in supplemented subjects whose pregnancy rate was 45.8% compared with 22.9% in unsupplemented subjects (7) (n=215). In our own research comparing a small group of subjects with unexplained infertility with age-matched normal fertile controls we found a correlation between infertility and the selenium:cadmium ratio with infertile subjects having low serum selenium and raised whole blood cadmium, which was statistically significant despite the small size of our sample (8). In our survey of pre- conceptional supplementation (n=130) 50% of a sub-sample (n=42) who were preparing for IVF were taking only folic acid 400 µg daily but 14.2% were taking a mineral and vitamin supplement that was very similar to the Rumiris et al mineral and vitamin supplement detailed above. We compared our data for total nutrient intake (dietary + supplemental) with the recommended daily intake for early pregnancy and found that intakes were suboptimal in 50% of the subjects for selenium, zinc, magnesium and iodine and borderline deficient in 50% of subjects for vitamins B12, C and E, β-carotene, iron, folate + folic acid and essential fatty acids (8). Indeed, borderline low iodine and selenium deficiency are known to have an adverse effect on ovulatory performance (2,9). While we recognise that nutritional status is only part of the explanation for “unexplained infertility”, it would seem wise to take steps to optimise that status when veterinary and animal evidence for its importance is so strong. Yours sincerely, (1) El-Toucky, Khalaf Y (2008). Treatmant of unexplained infertility – should he tailored to the patient’sexpectetions, centre’s experience and available resources. BMJ;337(7666):362-363. (2) Hostetler CE, Kincaid RL, Mirando MA (2003). The role of essential trace elements in embryonic and fetal development in livestock. The Veterinary Journal;166,(2): 125-139. (3) Jauniaux E, Watson AL, Hempstock J, Bao Y-P, Skepper JN, Burton GJ, (2000). Onset of maternal arterial blood flow and placental oxidative stress: A possible factor in human early pregnancy failure. American Journal of Pathology;157(6):2111-2122. (4) Guerin P, El Mouatassim S, Menezo Y (2006). Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Human Reproduction Update 2001;7(2):175-189. (5) Rumiris D, Purwosunu Y, Wibowo N, Farina A, Sekizawa (2006). A Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status. Hypertension in Pregnancy;25(3):241–253. (6) Stovell A, Matar R, Winston R Eyani L, Ward N (2000). Human infertility and environmental heavy metals: lead cadmium and zinc. Proceedings of the fifth international conference on environmental pollution, Ed A Anagnostopolousmith; Publised by Korakidis, Thessaloniki: 318-324 (7) Matthews S, White KL, Sutcliffe AE, Parsons WJ, Rutherford AJ, Sharma V, Picton HM, Hay AWM (2001) . Multivitamin supplements are associated with an increase in follicular fluid antioxidant levels and appear to improve outcome in assisted reproduction. Human Reproducrion;16(S1):151 (8) Nichols JAA, Curtis EPP, Rayman MP, Taylor A (2008). A survey to estimate total nutrient intake at conception — Dietary and supplementary. Journal of Nutritional & Environmental Medicine; 17(1): 12–43. (9) Wynn M, Wynn A (1998). Human Reproduction and Iodine Deficiency: Is It a Problem in the UK? Journal of Nutritional & Environmental Medicine;8(1):53 – 64 Competing interests: None declared |
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