Clomiphene citrate (Clomid) can help women with anovulation to ovulate but often has the undesirable side-effect of thinning the uterus lining. This unfortunate side-effect of Clomid may reduce the chances of implantation and increase miscarriage rates; by the same process cervical mucus can be reduced which may impede the sperm’s movement towards the egg. Having a thicker uterus lining is correlated with better pregnancy rates and lower miscarriage rates in other studies highlighting the fact that Clomid's thinning effect may be connected to implantation failure and miscarriage.

Clomid adversely affects the uterus lining through it’s anti-estrogen activity which is helpful in that it produces a surge of FSH to stimulate follicle development but unhelpful when the estrogen needed for the uterus lining and cervical mucus is blocked too. An American study - published in Human Reproduction - tested the theory that suppositories of extra estrogen applied close to the uterus may overcome this problem.

This study randomized oligo-ovulatory (irregularly ovulating) women into four groups who received either:

* 50 mg of Clomid from day three-eight either with or without hormonal support

* 100 mg of Clomid from day three-eight either with or without hormonal support

The hormonal support consisted of estradiol suppositories (E2) 0.1 mg twice a day from day eight until the LH surge followed by progesterone gel applied close to the uterus as directed beginning three days after ovulation. All the women had an endometrial biopsy ten days after ovulation.

The endometrial biopsies were very revealing showing that the women who received hormonal support had uterus lining which were 'in phase' and showed "complete predecidual changes" indicating that they were perfectly ready for implantation. About half of the women without hormonal support (4/6 and 3/6) did not show the predecidual changes indicating a lack of readiness for implantation leading the researchers to conclude:

"The addition of...E2 (suppositories) and progesterone to CC (clomiphene citrate) ovulation induction regimens normalizes the alterations in endometrial morphology. Hormonal treatment combining...E2 (suppositories) and progesterone may improve endometrial receptivity in CC cycles and ultimately yield higher pregnancy rates."

If you have been unsuccessfully trying to conceive with Clomid try asking your physician if you can try a hormonally supported Clomid cycle to see if it makes a difference.

This article is intended for informational purposes only and is NOT intended to diagnose, offer medical or nutritional treatment or replace medical or nutritional advice for which you should consult a suitably qualified physician or dietitian.

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Ref.

Hum Reprod. 2002 Feb;17(2):295-8. Sequential hormonal supplementation with ....... estradiol and progesterone gel corrects the effect of clomiphene on the endometrium in oligo-ovulatory women. elkind-Hirsch KE. Phillips K, Bello SM, McNicho M, de Zeigler D.