ABC of Tamoxifen as ovulation inductioin

“Tamoxifene

Tamoxifene: - The theoretical advantage of TMX over 1) CC is that it (TMX) does not exhibit any antiestrogenic effect on cervical mucus or endometrium. As such, many specialists use this drug (TMX) in cases of CC failure (sometime in CC resistant too) - where there is a persistent thin endometrium in previous CC cycles.

2) As an alternative to Gonadotrophins as a treatment modality o thin ET:-Honestly speaking, TMX, so far my belief goes, is occasionally used where couple can’t afford for gonadotrophins.

 Tamoxifene is a SERM. Like Clomiphene this drug too was initially used for breast cancer. Tamoxifene has never been approved till date by any agency for Ovulation induction. (Source: Hum. Reprod 2005; 29:1511).

It is claimed that it (TMX) is as effective as CC in ovulation induction. It is initially used as 20 mg OD schedule. After two failed cycles with TMX (if there is no evidence of ovulation) -the dose of Tamoxifene can be increased in a stepwise fashion upto 60mg OD.

It is more probable that endogenous hormones become near normal in pre-induction phase.

I think if ET is more than 5 mm, better to induce withdrawal bleeding before ovulation induction.

 The other alternative option is if on day 3 - ET is > 5 mm. then one can possibly reschedule evaluation of ET after 48 hrs...In some cases, however, on day 4 /5 ET may shrink down to expected 5 mm by waiting for 48 hrs. Therefore, one can possibly gainfully utilize that cycle too by initiating CC/tamoxifen/i.e. on day 5. ET may regress to 5 mm.

Tamoxifene: - The theoretical advantage of TMX over CC is that it (TMX) does not exhibit any antiestrogenic effect on cervical mucus or endometrium. As such, many specialists use this drug (TMX) in cases of CC failure (sometime in CC resistant too) - where there is a persistent thin endometrium in previous CC cycles.

 Honestly speaking, TMX, so far my belief goes, is occasionally used where couple can’t afford for gonadotrophins. Tamoxifene is a SERM. Like Clomiphene this drug too was initially used for breast cancer.

Tamoxifene has never been approved till date by any agency for Ovulation induction. (Source: Hum. Reprod 2005; 29:1511). It is claimed that it (TMX) is as effective as CC in ovulation induction. It is initially used as 20 mg OD schedule. After two failed cycles with TMX (if there is no evidence of ovulation) -the dose of Tamoxifene can be increased in a stepwise fashion upto 60mg OD. 

 Tamoxifen when? Scope & Indications of Tamoxifen as Ovulogens:-:- In present day the main and possibly the only indication of prescribing TMX is when there are side effects with CC particularly visual /neurological side effects . Scintillating...

 Tamoxifen is the second choice in CC resistant cases. Better option will be Gonadotrophins. Gonadotrophins are quite effective in CC resistant cases but costly and requires rigorous monitoring. Such facilities may not be available in rural settings. There remains a scope of TMX in selected cases of CC failure/ resistance cases.

CC has failed after couple of cycles. Now, what are the practical options open to young women in Indian perspective? Once counselling done after several cycles of failed CC, many Indian couple (even uneducated couple) do realize that gonadotrophin is badly needed for them but repent because they are simply unable to afford for G cycle. Put in such a situation (after CC resistant cases) the option remaining to the treating physician to prescribe TMX (as an alternative to Gonadotrophin) and make some compromise. Doctor feel-“Watch- what happens”-.

 Ours is a resource poor country: Not to speak of cost of purchasing Gonadotrophins: Many Indians even cannot afford common low cost fertility tests (PRL,) that usually should precede CC therapy (tests for medical fitness of pregnancy- IgG rubella, hepatitis Viral Screen, TSH, etc). Not to speak of tests prior to initiation of Gonadotrophin—which is the preferred agent most commonly used after CC failure/ Resistance. Not all such tests are done free of cot in Govt/Municipal Hospitals.:--Unfortunately, many Indian couple cannot afford for usual tests at this juncture - so as to why CC failed in their case.

 Such tests, if not carried out earlier are 1) AMH .2) AFC, 3) Insulin Resistance, 4) high D2 LH & testosterone 5) DHEASO4, & 6) PRL --not to speak of other costly tests. In such cases further tests so as to find the etiology of CC resistant in particular women. We, Indian doctors have to make many compromises at every step of clinical practice not only in the discipline of reproductive medicine.

 Like CC TMX is also an competitive estrogen Antagonist –TMX ,like CC also competitively block the estrogen binding sites at the level of actuate nucleus of hypothalamus, and stimulate GnRH receptors located at Pit for accentuated release of pit FSH & LH.

 Is there any differential expression of LH over FSH –particularly in CC failure cases? In fact there is about 3-4 fold rise of FSH & LH while someone is on CC.

 But the differential expression FSH & LH in the aforesaid two types of oral Ovulogens is still under study. I have a feeling this part of CC /TMX have not been adequately explored. It is hoped by many researcher that CC failure is due possibly to over expression of LH in fair number women and is a major cause of CC failure poor oocyte quality.

Those who are biased for TMX they claim such disproportionate rise of LH on cycle days 8-11 is not the case with YMX.

I admit that I personally do not know about the differential expression of FSH vs. LH in CC cycles against TMX cycles. But many researcher believe that CC in fair no. of cases more rise of LH during the cycle days of Day 8-Day 10thereby interfering the oocyte quality. Similarly in some cases of CC induced cycle serum E2 remain at supraphysiological levels –explain partly the reasons of failure of CC cycles.

 In such women one can use TMX as an iterative if the age of the female partner is< 25 yrs or she cannot afford for gonadotrophin cycle. Some also have claimed that LUF is more than TMX.

 Why oral Ovulogens in lieu of gonadotrophins in CC resistant/Failure cases??- The advantages of CC/ Tamoxifen are low incidence of multiple gestations, OHSS, low cost, minimal monitoring, .But we are all aware of the fact that whatever agent we use in fair number of subfertile women CC/TMX become resistant despite appropriate dosage e.g. Ov insufficiency, Hyperandorgenism, Insulin resistance, Elderly women and women with BMI> 30 Kg/M2. In such cases one prescribes oral Ovulogens mostly CC but the doctor concerned is sceptical right from the beginning that CC/TMX may not work.

Miscarriages rate and multiple pregnancy:--Such rates are more or less same with CC and Tamoxifen :- e.g. 10% & ABOUT 22% RESPECTIVELY DEPENDING ON OTHER ASSOCIATED FACTORES LIKE Age of female partner, BMI, ANDROGEN EXCESS DISORDERS, Hyperinsulinaemia, serum testosterone etc etc.

But for the oral Ovulogens to be effective the D2 serum E2 should be ideally> 50 pg/ml and not less. 

Additionally. Women why are contraindicated for CC may also be a given few cycles of TMX RY after due counselling. Such contraindications of CC are impairment of hepatic enzymes.

 Tamoxifene:-
There are two important advantages of Tamoxifen over CC. These are

a) No anti-estrogenic effects of CC on genital tract b) No recorded neurological abnormality as seen very occasionally in CC cycles. Abnormalities of vision, the rare occurrence depression, grand mal epilepsy and hallucinations are not heard of with TMX.
Additionally, researchers working with TMX and CC: - also claim that the very rare threat of Auditory nerve changes in CC induced cycles is nonexistent in TMX cycles.

These are the advantages for choosing TMX over CC. At least such plea has been put forward by different researches in last four decades. But by convention, globally, (including myself) CC is most popular agent for Ovulation induction.

Moreover use of TMX in Ov induction is an “off-level use “–as I mentioned at the outset. `