Polycystic ovarain syndrome associated WITH INFERTILITY

Basically all subfertile women fall into two major groups, be it PCO or non PCO group. I follow that principle and firmly believe that such basic clinical classification is  an very useful in day to day clinical practice and formulating investigations in  right directions. : You may follow that to minimize the cost of investigations and focus more on earlier definitive pathology. For instance  in women with definite Pel lump or uterine fixity/ thick parametrium/ nodules in POD –a detailed endocrine evaluation seems of less importance to me.  Those women who didn’t exhibit any mass/ fixity/nodules fall majority of subfertile women (Group A women) and my assumption that such women are major group (about 80% of all cases of subfertility) I personally level them as  Group A women.

Part III:-Group A:  One note of caution: No hurry in HSG / SIS in Indian context where Genital Kochs is common though I shouldn’t call it as rampant this procedure should be deferred as the procedure can flare up a tubal pathology and aggravate the tubal factors of subfertility which is often difficult to diagnose .  However, In absence of any palpable pathology, or visible Cervical lesion uterotubal evaluation should be deferred and only to be done after following interventions like

 Intervention 1: To be    initiated only after 1 yr of trying and after normalization of BMI, life style modifications as appropriate  and correction of any medical disorders, if there be any .

Relevance of basal sacn:-Routine day 3 USG is very important, ovarian morphology in particular. Any hydrosalpinx should be noted. .It often so happens that when the couple comes to you (consultant) then a basal scan has been performed .You have to see plate yourself.. One should add L Methyl folate, correct anemia, complete the immunization if due, should insist on  deworming if clinician  considers essential .To conclude the first phase if tr , I must summarize  by saying 1) To suppress PRL is level is > 35 or clinical evidence of Galactorrhoea (current terminology  is “Inappropriate lactation” and Metformin according to your conviction & judgment.

Take care of associated minor endocrine aberrations like raised PRL,  high  TSH, Raised DHEAO4 & insulin resistance . Meanwhile to keep TSH < 2.5 IU/ml. Vit D suppl (insulin sensitizer like Myoinositol)  if indicated. Stress free life, Brisk walking in morning / evening at small lanes of your locality /. Open parks/ Fields/ or at least at your roof.

Extra steps for Lifestyle modifications:-Listening to sings and game of your choice and weekly once/ monthly once  visiting  to religious places of your locality temples will go a  long way to make HPO axis ,Hypo- Pit-Adrenal axis normalization, . All these steps helps “Pineal body amygdaloidal nuclei” -- and their subordinate staff i.e. hypothalamus in an ordeal way (harmony) . All these procedures relaxation by   1) playing game of your choice, 2) listening to music of your choice/ reading story books.3) Other   Life style modification, 4)  visiting religious places once a week/ month will rectify the  Lock Down  imposed by hidden stress in your body –Amygdala  nucleus becomes irritated and cause abnormal firing-> abnormal GnRH pulses by hypothalamus.   These steps are at no cost but more important than ovulation inducing agents. These five steps are like to please Lord Shiva of Hindu mythology (the amygdaloidal nucleus and six common Neurohormonal including serotonin) . I am sure that if one can adopt such steps amygdala nucleus is bound to be in order . As a result then other nuclei in the midbrain will be compelled to control  their abnormal firing(neuronal impulses)  in the form of excess / idle GnRH  pulse frequency  and amplitude and Corticotrophin impulses will be  over if one can satisfy amygdaloidal nucleus .

.Intervention 2 : This step ideally  correction of abnormal life style. However this chiefly comprises of three cycles of ovulation induction which should be by Letrozole (first cycle 2.5 mg) and second cycle 5 mg tab for 5 days initiating from Day 3;. If conception don’t ensue after  2-3 cycles of letrozole(monitoring by Fol monitoring, LH kits  are often yield poor prediction as is self Cx mucus tets-Spinnbarkeet tests-long thread of say 6-10 cm followed by thick small thread of Cx mucus between her finger tips.)  After lifestyle modifications, and 3 cycles of Letrozole it  will be our duty to insist on HSG Vs SIS if she is aged 26 yrs and TT(trying time is > 3 yrs) .By and large the working rule is to insist on HSG(or say SIS) after couple of cycles of  ovarian stimulation which are non gonadotrophin. My feeling is that if  one  proceeds for gonadotrophin cycles then ideally  such stimulated cycles should follow tubal evaluation. This may be either by traditional HSG or better by Saline Infusion sonography.(SIS) .

Part IV. Why Saline Infusion sonography is preferred??   In my opinion, SIS should be  done by an expert sonologist as day care procedure and this procedure has an edge over HSG because  polyps, small myoma, adhesions (Ashermans ) are better diagnosed by SIS . This is   my personal opinion, I may be wrong as well. Hysterosalpingography (HSG) has been used to evaluate the uterine cavity and the tubal status since decades. It uses iodinated contrast and X-rays and is painful and inconvenient for patient. Laparoscopy is considered to be the gold standard for tubal evaluation, but is an operative procedure and needs anesthesia. Though conventional ultrasound is a modality of choice for assessment of uterus and ovaries, it does not allow assessment of the fallopian tube unless there is any fluid surrounding it or inside the lumen. This fluid interface can be created artificially by introducing saline in the uterine cavity and fallopian tubes and scanning simultaneously.

The procedure is named Saline infusion HSG. Saline infusion sonohysterosalpingography (SIS) can be done with B mode US and Doppler. SIS can demonstrate a patent tube but if blocked, the site of block cannot be demonstrated.

 Part V. What do we mean by “hystero-contrast sonography (HyCoSy) ?  Ultrasound contrast agents can be used for tubal assessment using contrast mode on the scanners. This procedure is known as hystero-contrast sonography (HyCoSy). This actually shows the passage of hyperechoic contrast agent through tubal lumen and delineates it and locates the site of block. Using the volume ultrasound may even make the demonstration of tubal status and fimbriae better. Results of HyCoSy have been found to correlate well with laparoscopic findings, which are a gold standard. It is recommended by National Institute for Health and Clinical Excellence as a primary investigation for tubal assessment in patients without any positive history of tubal damage and also can replace a second look laparoscopy.

 I also have a feeling that these three uterine conditions (synechiae, small polyp/s or small submucous myoma) collectively account for about 7-10% of all cases of F subfertility. All these minor conditions are difficult to palpate clinically and often missed in traditional HSG. Such conditions which chiefly result in implantation failure or result early embryonic demise due to unreceptive endometrium.

Part VI. My answer to her (Ex PGT) : Subfertility with PCO how to investigate & Tr in Indian context?? ::Routine evaluation: I assume that subfertile couple who come to under your treatment   has 1) normal seminal parameters with 2) normal sexual relation(availing fertile days at least for 1 yr for women < 30 yrs & trying time should ideally be < 6 months in women above 30 yrs,)  .  For each type of subfertile women you quoted it will be better to plan the treatment according to her age & months of trying. I also presume you have assessed medical fitness for pregancy, in the sense of Viral screening, STI screening, Hepatitis serology and above all complete haemogram & ruled out Haemoglobinopathies. A Pap smear is appropriate as is Basal Scan on day 3-5 in non-induced cycle, Ovarian volume estimation, its echo structure and  AMH History immunization and  past medl or surgical history should be elicited , Drug abuse, life style , dietary habits and above all stress can be evaluated with some patients without hurting the couple. Regular intake of drug has to be enquired,. Any past history of miscarriage have to be enquired and cycle regularity and recent weight gain should be enquired. Family h/o Diabetes carries a risk factor for hyperinsulinaemia in fair number of cases. In such women life style modification and 3 yarely lipid profile estimation, LFT profile should be recorded and preserved in her diary.

. But admittedly not all these tests are done in all cases just  for financial reason , though all such tets are noninvasive in  nature .Such screening procedure is uncommon in most of the rural centers as is uncommon is CBE(Clinical Breast Examination on annual basis after the age of 40yrs).

Part VII:  interventions 3: If lifestyle & BMI is controlled and Letrozole have failed then as mentioned earlier SIS/ HSG should be performed. However in cases of adnexal mass / fixity of uterus Lap Hyst procedure should be planned at an earlier date and letrozole induction may be planned after Lap hysteroscopy   then after a course of antibiotics for PID (chlamydia  related drubs) she should be offered .

PART VIII : The role of Lapraohysteroscopy and in most cases pelvic  adhesions of nonspecific nature will be observed or endometriotic spots  of varying degrees will be visualized and video recorded. In type B cases HSG or SIS(saline Infusion sonography)/ HSG  should better be avoided.  Endometriosis is a common cause as is Kochs. A low threshold for pelvic antibiotics, exclusion of Kochs & STI and Tr of Chlamydial infection seems rational and worthy. In fact , though seems illogical often prescribe drugs for chlamydia to both partners on empirical basis( not supported by any  academic bodies) .

Part : IX:-Type B cases (say 20% cases) Subfertile women with palpable pelvic mass / Fixity :

Your third type of  couple: 3.Pt who tried 3 OI,1 IUI, with  irregular cycles. How to work them out? “Ans: As because her cycles are irregular most likely there are some endocrine disorder is there and unless that is diagnosed and rectified it will be difficult for her to conceive. Try to normalize insulin, androgens and PRL, TSH ,etc . Having said that If she is aged > 30 yrs then ART will be better option. The causes of IUI failures are 1) Minimal endometriosis which was unsuspected with resultant poor quality oocytes, and failure to fertilize or poor onward growth potential of fertilized ova  to progress beyond blastocyst. 2) Local endometrial pathology 3) abnormal sperm functions, morphology in particular 4) suboptimal training of  staff deployed for sperm prepn techniques. 4) Faulty/ poor quality media delayed servicing of incubator or centrifuge machine.

Part X:-- Semen analysis is often done by  Hemocytometer method, rarely by Makler's chamber(costly approx Rs 32,000/-) , Micro Cell.  Laminar flow is not essential but will add to the result as is change of IUI canula. These have to rectified in consulation with your senior known colleague to whom U personally are acquainted.