Tips to achieve success in ovulation induction by clomiphene , Letrozole or tamoxifene.

Part=3 of ovulation induction. How  best to help the  subfertile=Respecting her wishes. Up to the decades of fifties of twentieth century people used to construct buildings without the help of engineers. But now everyone take help not only of engineers but also interior decorators. The doctor who is planning ovulation induction even  with  oral agents (not gonadotropin cycle)   act as engineer only but I must say that it is his/ her dedicated  team of endocrinologist /Path Lab/ Sonologist in particular are the “Interior designer” . Am I speaking rubbish?? I am not a cool minded person. Most members are aware of my know that. But planning of ovulation induction (oral obvulogens) warrants a cool brain.  Why planning of ovulation induction is gaining importance?

 Ground realities are followings:-.

Use of body weight to select the initial dose of CC or TMX

The dose of CC and by inference TMS, necessary to induce ovulation is proportional to body weight .A starting dose of 100 mg CC or 60 mg TMX is recommended for patients who weigh > 165 I (75kg). A starting dose of 25 mg CC or 10-20 mg TMX is recommended for women who weigh < 100 I (45kg).other weights should be started on 50 mg CC or 20-40 mg TMX.

Use of mid-luteal progesterone to select the dose of CC or TMX

Progesterone levels in the mid-luteal phase of CC cycles that result in term pregnancies average 37 ng/mL, compared to 22 ng/mL in spontaneous cycles [19]. Progesterone levels in the mid-luteal phase, 5-7 days after ovulation, that are less than 18 ng/mL   are evidence of possible luteal insufficiency. Levels less than 15 ng/mL   are rarely associated with ongoing pregnancy. When progesterone levels are less than 18 ng/mL following CC, oral or vaginal supplementation (see notes regarding basic protocol) should be considered in the current cycle, and the dose of CC or TMX should be increased in 50 mg and 20 mg increments respectively in subsequent cycles until progesterone levels are ≥ 18 ng/mL

Please do interrupt me as I progress on Ovulation induction:-:-Not all doctors have changed:-Not all are known:-

Effect of increasing the dose of CC or additional days of treatment

Increasing the dose of CC from 50 mg in the first cycle to 100 mg in the next cycle results in minimal increases in average number of small, medium and large follicles (≥ 12 mm from 2.4 to 2.6, ≥ 15 mm from 1.7 to 1.9, ≥ 18 mm from 1.2 to 1.3) [18]. Extending the number of days that 50 mg of CC is taken to 8 or 10 days has been shown to result in ovulation in patients who did not respond to 200 or 250 mg CC for five days in a small serried .The benefit of increasing the dose of CC or number of days CC is taken must be balanced against the possibility of increased antiestrogen effect on the endometrium and cervical mucus. The effects of increasing the dose of TMX or extending the length of TMX treatment have not been reported, but they would not be expected to have an adverse effect on endometrium or cervical mucus. When additional numbers of follicles are desired, increasing the dose of CC or TMX will have little effect compared to adding or substituting gonadotropins .

Use of preovulation ultrasound (US) to predict ovulation and multiple pregnancies

Preovulatory US performed 5-7 days after the last CC or TMX allows the ovulation day to be predicated for timed IUI or intercourse, and the number of preovulatory follicles to be assessed in order to cancel cycles if an excessive number of preovulatory follicles are present.

        In CC and TMX cycles the lead follicle is usually 18-20 mm in diameter on the day of spontaneous LH surge and 20-24 mm on the day of ovulation. The dominant follicle and others destined to ovulate ordinarily increase at a rate of 2 mm per day from cycle day 10 until ovulation. The size of the leading follicle on cycle day 12-14 can be used to predict when a spontaneous LH surge and ovulation will occur. If predicted to occur at an inconvenient time for performing IUI, ovulation can be induced by HCG (5,000 or 10,000 IU) or rhCG 250 mg if the lead follicle is at least 16 mm and estradiol concentration is consistent with the number of follicles. The serum estradiol level should be 180-250 pg/mL per mature follicle.

            The possibility of multiple pregnancies can be estimated from the number of follicles expected to be ≥ 10-12 mm on the day of spontaneous LH surge or HCG injection. This allows sufficient time to proscribe intercourse or cancel IUI if there is risk of triplet and higher-order multiple pregnancies or a desire to avoid a twin pregnancy. The probability of any pregnancy in CC cycles is most closely related to the number of follicles ≥ 15 mm, rather than or smaller or larger sizes . Multiple pregnancy rates in CC and TMX cycles are most closely related to the number of follicles ≥ 12 mm on the day of spontaneous LH surge or HCG injection, but follicles as small as 10 mm on the day of HCG can result in pregnancy Pregnancy rates do not increase appreciably when there are more than four follicles ≥ 15 mm in CC cycles. WHO class II anovulation is most Hypo-Pit_gonadal dysfunction.And ovulation induction by CC/Letrozole /Tamoxifene .My dear members please be aware that most of  us don’t know anything about PCO but endocrinologist know all of it including clinical the subtypes & phenotypes of PCO/ its  foetal origin, adolescent expression, associated menstrual  disorders, gain in weight, subfertility poor oocyte quality. In later life onset of   HTN, Dyslipiadaemia, hyperglycaemia, hypercaoguable state atherosclerosis, CVS strokes and endometrial Cancer. With these few introductory words let this old man imitate the ball rolling on Ovulation induction. To believe this ordeal for simple induction or NT to follow is your business. Please remember absence of evidence is not evidence of absence. And the more we gap on chatting more we acquire Expansion of Knowledge: 

 What are the tricks of the trade,

Collectively, one should :-Use of preovulatory ultrasound (US) to evaluate endometrial receptivity

Preovulatory US enable evaluation of endometrial receptivity by measurement of endometrial thickness and observation of the endometrial pattern. Ideally, endometrial thickness will be ≥ 9 mm, and endometrial pattern will be triple line on the day of LH surge or HCG injection .If the endometrial thickness is < 9 mm on preovulation ultrasound, administration of HCG should be delayed. If the LH surge has already started, vaginal estrogen (2 mg micronized estradiol tablets or the equivalent twice daily), or oral estrogen (2 mg micronized estradiol tablets or the equivalent four times daily), can be used provided that hCG is given to induce ovulation, lest the estrogen suppresses the LH surge, whether adding estrogen increases endometrial thickness is unproven. Thickness normally increases at a rapid rate in the late proliferative phase of CC cycles as the endometrium escapes the antiestrogen effect of CC, and eventually equals or surpasses thickness in spontaneous cycles .In subsequent cycles endometrial thickness may be improved by using a lower dose of CC, by switching to TMX, or by taking oral or vaginal estrogen (2 mg daily) concurrently with and following CC.

Medical Wisdom:-Use of serum LH monitoring to predict ovulation day:If a baseline LH has been measured at the start of the cycle, a repeat LH measurement on cycle day 12-14 will provide an indication of how soon spontaneous ovulation will occur. Ovulation normally occurs within 24 hours from the time that LH levels are twice the baseline level. A smaller increase above baseline level indicates the beginning of the LH surge and ovulation in 36 hours. A sharp dip in serum LH is often seen one day before the start of LH surge and ovulation in 36 hours. A sharp dip in serum LH is often seen one day before the start of LH surge. In PCOS patients, LH levels are often ≥ 20 mIU/mL during the early follicular phase but decrease to < 10 mIU/mL one or two days before ovulation and rise again at the beginning of the LH surge. Repeated LH determinations combined with US and estradiol levels may be needed to determine when the LH surge starts in PCOS patient.

Use of human chorionic gonadotropin (HCG) or recumbence HCG (rhCG) :-Use of HCG or rhCG in CC and TMX cycles is seldom necessary to induce ovulation. It is used in cc and TMX cycles to induce. It is use in CC and TMS cycles to induce ovulation at a time convenient for IUI or TI. Use of HCG or rhCG does not increase the incidence of multiple pregnancies. Bottom line is the more you use  condiments ( monitoring of cycle by day 3= E2,Prog estimation , backed up by  stringent Foll monitoring, timely HCG, Endo thickness, Endo/ Follicular  lagging in relation to day of stimulation  ) are key to success of ovulation induction in even in CC/letrozole or Tamoxifene not to speak of gonadotropins only.!!