LUF-Luteinized Unruptured Follicle --LUF causes, How to overcome & treat LUF

The Role of Trigger in CC/ Anastrazole cycles with or without IUI ? 

We have never asked ourselves what LUF is & what may be aptly termed as iatrogenic LUF by triggering in CC/Letrozole cycle!!! What is LUF?? : The Luteinized unruptured follicle is enigmatic condition with very little literature on it. Honestly speaking we, the clinicians too read, discuss & search literatures on this topic very little.  Why?  Because this condition remains unrecognized unless Follicular monitoring  us continued till late in luteal phase which we  often omit for financial reason. Sadly,

LUF often pass unrecognized in stimulated cycles (be it CC/ Letroz). It is no point denying that -majority if clinicians stop Foll monitoring once DF is 17 mm (as  recorded by FM) for most of OV induction. This is a common practice and is more commonly observed in mofossil  areas.   This non-monitoring after achieving 17 mm is true for even for IUI cycles (post trigger) 

. By contrast if nonrupture is detected ( no ovulation  with hCG) 5000 (hCG given while DF reaches 18 mm) then in that cycle no preg occurs. If the cycle is not monitored in luteal phase we falsely implicate that in that CC /Letrozole is a CC failure which is partly true.  But conscientious or dedicated center will always insist on FM after a trigger (post hCG  48 hrs) or even lain CC/ letroz cycle without trigger (non IUI cycles) . Many a times, a TVS done after 48 hours shows an unruptured follicle between 22-25 mm. What should be done if Ovulation does not ensue even after trigger in an IUI cycle? The entire plan is lost if there was a monofollicular growth.  I am not sure but some school suggests a second higher dose of hCG of 10000 in teased cycle. Do members approve that (Reminding U members it is not double stimulation and Double trigger as is commonly dine at Japan) in ART cycle, I am talking of IUI cycle and LUF.

 If There is no evidence of rupture in a IUI cycle but the IUI procedure was contemplated with great hope only to find  later on day 22/23 that there is no classical CL but LUF. Can we at this phase help her in that cycle?? Some have suggested to push a second shot with HCG 10000 !! members view on this regard. In many cases there can be “Point-counterpoint evaluation” but that happens in medical line. People may differ.. Many encounter this problem of LUF but nothing can be done in that particular cyce. It is presumed that this is to be a cystic follicle and have never seen a pt conceive in that cycle. Does it recur? Ans: usually not . But such incidence of LUF is not consistent in further cycles.

LUF detected in that cycle as Foll Monitoring was  continued be it CC cycle or IUI cycle What are the options before us for  that cycle?

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Option 1.:-Cancellation of cycle if it becomes cyst.

Option 2:- One can use GnRHa trigger Buserelin 1 unit sc/ Leuprolide 1 mg sc.

Option (preventive):in second cycle

Option 3:- No trigger-be it CC/Letrozole cycle or IUI cycle.-Avoid any trigger and Luteal support in C /Letroz cycles:- It  is the standard policy “No trigger at all” to avoid LUF : The question is should we trigger in CC cycles ?  No. Because that may harm by converting a healthy D F to LUF . The reason of not suppl by HCG trigger in cc cycles are there is already sufficient endogenous estradiol and  LH surge mechanism is in operational.  Therefore if the follicle grows properly under the effect of CC/ Letroz, then let the nature pick up the timing for ovulation.

There is good evidence to suggest No role of trigger in clomiphene induced cycles for ovulation induction. hCG administration offers no outcome benefit over spontaneous ovulation in anovulatory women treated with clomiphene citrate.

My dear members, please make a routine policy to drag Fm up to 96 hrs after a  follicle is of 24 mm or after trigger in HMG cycle Should one insist on  post rupture scan ??

The post rupture scan can easily pick up unruptured follicle. When 50 mg CC patient, most of specialists prefer to leave them without any trigger or Luteal support. But few prescribes  trigger at >21-22 mm but  Ultrasound study is not done post trigger and the concerned clinician has a belief that the good quality DF must rupture ,This ego is wrong attitude about one’s misbelieves  ,Once he/ she changes his/her habit and  make a routine policy to drag Fm up to 96 hrs after a  follicle is of 24 mm or after trigger in HMG cycle he/ she  will surprised to see many cases do not ovulate in  spite of attaining  good follicle with or without trigger, The dynamics of rupture is still unknown. What about Luteal support??
  In subsequent cycle.  Third option of treating / avoiding LUF: Add Oxytocin as well:-Next time along with hcg 5000, one may add Oxytocin 5 units I m. Because oxytocin helps in extrusion of ovum. There is smooth muscle fibres in ovary which are stimulated by PGE2 secreted prior to ovulation under the action of pre ovulatory progesterone rise (speroff).   Making use of the concept s the basis for oxytocin in h-CG trigger.

·           Fourth Option: Some use cc stair step protocol and thereby avert LUF. In such protocol combination of hcg 5000 and oxytocin 5 u is used for trigger. The outcome of this protocol to avert LUF is fair. Most women under this cc stair step protocol will ovulate in  95-99% times .Fifth option:- Jump on to MOS (Minimal ovarian stimulation/Mild protocols ):--The other option if trigger causes LUF- - The other option of preventing LUF is MOS. What is MOS?? .It implies minimal ovarian stimulation/Mild protocols with Gonadotrophins mode of Stimulation. Changing to MOS (minimal ovarian stimulation) but one may add antagonist if suspecting premature LH surge. The debate continues and Jury is still not out. The question is which hormone causes Premature LH surge. So long we knew that it is LH which causes both timely (natural) and untimely LH surge (iatrogenic-poor planning). Now the finger  is points to FSH hormone . Who is the culprit for premature progesterone rise is still unknown.FSH or LH?
7. CC step up protocol may minimize recurrent LUF;

One can Follow up the unruptured follicle after 48 hrs, by then it might have ruptured or grown up to a cyst or show features of Luteinization. This simple follow up by USG will guide us to take a decision for an IUI. And then we can also check the efficacy  .The immediate pre HCG hormones are the same in normal adulatory and LUF cycles...so it is either intrinsic problem with follicle (granulosa cell dysfunction/ chronic inflammatory changes) or Hormonal changes in the follicular phase.It means that rather than altering the trigger the stimulation protocol has to be changed.  Some add Inj HCG 2000 in luteal phase when using Inj Leuprolide for trigger???
They have noted good results with hcg trigger but only if it ruptures. And found no result with Inj Leuprolide as trigger, though I added hcg in luteal phase.

 Sir then what could be the reason of no results with Leuprolide???

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What to do about trigger when combined CC & HMG is tried in IUI cycle ?

 One should exclude para-ovarian cyst in basal scan because that may confuse as LUF..  How the CC /Letroz cycle be monitored?? Clinical outcome alone is assessed, not even with midluteal P4 but next menstruation or pregnancy.

What are the ASRM practice committee guidelines? Ans:- Such committee recommends documentation of ovulation only in the index cycle for CC which can do by mid luteal progesterone as well. Need not monitor the subsequent treatment cycle.

  The downsides of (odds) of monitoring & Trigger? What we need to be stressed here is the impact of such repeated monitoring and blood test for first line treatment which is quite disruptive for the woman and  couples in many ways. Repeatedly coming to centre, waiting for ultrasound, intrusive tests- all this can take its toll. It doesn’t benefit the patient much but increases stress and indirect costs.

. What is the current view of Gynaecologists in general then?? The basic question remains unanswered regarding need for trigger. Surprisingly there is hardly any data to suggest that trigger works better than no trigger and only two trials were for OI with CC. It is equally true that world has moved on and  now people are of option  that trigger is a must and there are plenty of trials comparing urinary vs recombinant hcg as trigger for non ART cycles!!!

But in mild stimulation IUI cycles one usually  give 5000 urinary HCG at DF 18
Generally  most specialists don't recommend scan after trigger but sometimes scan is done because of patients concern and find a unruptured follicle seems like.   . If one uses at all then one has to push the trigger at  20-22 mm not at 18mm.

Trigger or no Trigger in IUI cycles:- For IUI we need to give trigger for timing it.

It s conceivable that that it's inconvenient for a woman  to come multiple times but at the same time scanning is cheaper if done at centre. So also a P4 level to document the Ovulation and sometimes one can do himself if anxious to know why CC not working especially in 3-4^th  cycle. If one uses trigger at all then one has to push the trigger at  20-22 mm not at 18mm.

·         Suppose in a cc cycle planned for IUI(though most of us have switched  over to HMG in planned IUI cycle) if hCG trigger   And if that doesn't work (5000k HCG in a CC cycle) then it's not worth repeating the hCG or giving analogue(for instance inj Decapeptyl  in next cycle. Such drugs won’t help too much. At this stage with LUF occurring in one –two cycles one should perform Diag lap to exclude endometriosis or Pelvic adhesive diseases . This study was undertaken to compare the effect of oxytocin and human chorionic gonadotrophin (hCG) on ovulation and conception. A total of 100 women with anovulatory infertility were allocated into two equal groups to take clomiphene citrate plus hCG or clomiphene citrate plus oxytocin. The size and number of follicles by transvaginal sonography determined the administration of hCG or oxytocin. The serum progesterone concentration was measured to provide evidence for ovulation. The ovulation and pregnancy rate of the two groups were compared. There was no significant difference between the groups with respect to mean number of follicles, mean follicular size and rate of ovulation in three cycles. The rate of pregnancy was higher in the oxytocin group compared with the hCG group (12% vs 4%) but it failed to reach statistical difference (p = 0.140). Mild pain was the only side-effect observed in the two groups. Oxytocin was found to be a viable alternative to hCG for triggering ovulation in infertile patients.: