Bad PCO : Who are difficult to stimulate to stimulate

What are bad PCO cases?? Introduction: It is not uncommon to come  across women where the destiny of the follicle is that when COS is implemented in  PCO bad PCO cases  do not progress inspite of cc+metformin, AMH more 7, each ovary having 35-40 tiny follicles. These are resistant PCO non IVF raised basal LH: Most of such cases have  high levels of testosterone , insulin and LH are collectively lead to  bad PCO. These  are highly resistant to stimulation or OI
COS resistant pco non IVF raised basal LH:
 Follicular growth arrest

Q.1.  What do we mean by “Bad PCOS”, in general terms? Ans: It encompasses a subset of PCO women who are resistant to traditional methods of ovulation by average gynaecologits like us who are not ART specialist.

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One can divide PCO cases in peripheral centers : into good PCO and bad PCO based on the perceived ease of stimulation or difficulty.

·         Q. 2: What are , then the common protocols that are used by us who are not ART specialist in peripheral centers day to day clinical practice??

·         Ans: The initial treatment are well known  to us and mentioned in almost all Text Books which we can understand and  can implement in general practice .Such measures are six in numbers like  1) Weight reduction , Life style changes, Yoga 2) metformin/Myoinositol, Vit D (as needed) , 3) multivitamins, sometimes 4)  Co Q to improve oocyte quality  5) letrozole /CC 6) to supplement Gonadotrophins 8 day  if there is follicular arrest on day 8 .Sometimes IUI is added after inj HCG as trigger but if too many follicles appear then better to cancel the cycle  or to pt for agonist trigger.

·         Step 2:-After two months of such therapy when optimum weight(BMI)  is achieved then we who are  not ART specialist will usually initiate Letrozole or CC or any one of  them supplemented by hMG from day 8 in there is follicular lag (low ET therefore as a consequence) .

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·         In good PCO (good responders we often succeed but to me it seems it is rational to supplement follicular monitoring concomitantly  to watch the events occurring at ovaries and endometrium. Well, one may argue whether folliculometry is that is cost effective? To me every futile cycle adds more to the existing reproductive depression.  So there is every reason to monitor the cycle at least from Letrozole  /CC cycle No 2:

·         Q. 3:  How we can pick up Bad PCO (resistant PCO ) well ahead and do justice to such couple and politely refereeing to higher center by investigating few simple tests  thereby without wasting time and money of the couple.

·         Such poor responders will be A) Age > 30 yrs B) Trying time > 4 yrs C) AMH> 8     D)   Large no AFC     E) Ovarian volumes of ? 15 ml    F) High Day 3 LH > 8 IU . My personal feeling is that any three of them are present in a given couple we should better refer the couple t ART experts. What is your feeling?

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·          Q. 5 .  . What ART specialist will do ?  Can we foretell who will be hard to stimulate (bad PCO) by commonly used drugs as mentioned .Such cases are tackled by any of the following means like A) OCP from D2 to D25 B) Leuprolide 50mcg 12 hourly D16 to D25 C) Gonadotrophins from D2 of following menses  . Principle is Optimal preparation before stimulation should be ideal!

 So briefly , the followings are adopted :-

·          1) Down regulation by GnRH agonist or by 2) OCP 3) only progesterone in pretreatment cycle  5) LOD (if LH > 10 & Free testosterone is high with high per centile Ovarian volume ) One caution. AMH pre drilling and post drilling should be done and rake of 4 should be adapted. This fall of AMH is like endometriomata surgery seeking fertility improving surgery .

·         Q. 6 : After evaluation & Pretreatment what next about the mode of induction?? After having dome pretreatment as mentioned,  my presumption is that  they will categorize cases suitable for IUI (by hMG/r-FSH)    or recommend ART straightway depending on the A) age of female partner B) trying time, C)  AFC,  D) Serum LH as mentioned earlier.  . I confess I have no knowledge and wisdom how they do such categorization is done by ART specialists but fact remains a fair number of bad PCO where initially succeed with IUI. Only few of them have to be converted to IVF due to development of multiple follicles by gonadotrophins even if concomitant agonist are used along with r-FSH( Recagon ) when the lead follicle is 14 mm.

Q.. 8: What pretreatment they adopt based on reports of our center??

Such are in addition to down regulation by agonists/OCP/ only progesterone one can recommend for ovarian drilling followed by one course of Leupride for suppression before starting stimulation COS(controlled ovarian stimulation).

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·         Q. 9 : What is Chr low dose protocol in bad PCO designed for IUI? One would consider a low dose step up protocol in such cases. Starting as low as 25 IU or initiate with 37.5 IU × for 10 days without any anxiety and without monitoring. The first FM (follicular monitoring is done on day 10 of stimulation (cycle day 3+10)=13 day) . Thereafter if lead Follicle is >  12 mm then there are two thoughts 

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·         School-1: some prefer to continue to with same dse( i e “starting dose”) - hoping that this is the threshold dose will work for another 5 days and reassess on stimulation day 16 and may increase the dose thereafter. If no increment of lead follicle or poor growth lag then the daily dose of gonadotrophins is raised to 50 IU daily and reassessed every 5 days. Most of bad PCO will respond by monofollicular growth.

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·          Second School of thought :2: To increase the dose  Maintenance  dose  when lead Follicle  is 12 mm after 10 days  one can increase the dose  to 50 units for 5 days and then 62.5 IU till lead Follicle is 16/ 18 mm when hCG 10000 is administered.

Q. 10 .Why chose Chr low dose in Peripheral centers specially where couple can’t go to higher centers for long distance r family reasons? Ans: to subject patients for such high cost of gonadotropins ending with results much inferior to Ivf is less suitable for our patients

would consider a low dose step up protocol in such cases. Starting as low as 37.5 IU running for 7 days before serially increment. Next would be 75 IU at least for 4 to 5 days. This is till I find one two or maximum 3 picked up GF. Only then, I start growing them. That too slowly with increment doses. The patient may not respond or would at the end of , maybe 20 or 25 days. This knowledge gives me a feel good to take them for IVF if ever they fail to conceive. Some of these cases have been converted to "Rescue IVF" , when the response exceeded 3 or equal to 3.

·          There is no threat of OHSS in this Chr low dose protocol and reasonably suitable for peripheral centers. Seldom one has to refer the such pt to higher center for conversion to IVF cycle if at all to may follicles appears and OHSS occurs which is a safety valve protocol for peripheral centers, But it should ideally flowed by IUI. To me it appears only those centers who have such facilities for IUI may adopt Chr low dose protocol.

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·         Q.11: Well , I shall follow Chr low dose protocol But what kind of gonadotrophins? Ans: Opinion differs .Though most are in favour of r-FSH pen (hormone self inj like insulin-if she/ her husband can read English  ) but few have claimed results  are identical with low cost hMG as well, They also claim it is “how many days one can maintain with threshold dose patiently . It takes long 10-20 days  to initiate and achieve Follicular dominance of say 12 mm . But by and if base line investigation reveals high LH > 8 in basal evaluation (evaluation cycle) on spont cycle most of ART spl will opt for r-FSH pen(interested readers may read a cheap book written by Ro H0mburg, Title of the book “ Ovulation Induction and Controlled ovarian stimulation” Springer  publications at pp87-p95:chapter 9.Second editions. .

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·          ovulation induction with r-fsh.

·         But if such a bad PCO is selected for ART then most ART people  will discourage HMG as it contains LH . They don't think HMG is a good option for bad PCO.
particularly where previous cycle after resistant pco non Ivf cycle  with raised basal LH have failed. :

 Over days, cost is much less. Because given total Gonadotropins is far less. Then USG can be spared for many days. They can instead have urine LH kit. using rFSH gives certain advantages in such cases.