Intra Uterine insemination

 How helpful is Gonadotrophins & IUI  in Unexplained  Infertility & Oligozoospermia –the two chief indications for so called unexplained subfertility ?

A)                    Use Gonadotrophins in Unexplained subfertility along with IUI –is it a good option??  Ans: A recent   Cochrane  review  focused on this  issue examined six randomized controlled trials comparing IUI versus timed intercourses in both stimulated and unstimulated cycles of unexplained subfertility and three other trials in which the efficiency of IUI  in a spontaneous cycle  or combined to ovulation   induction were compared    . The authors   concluded that IUI with ovarian stimulation  increases   the live  birth rate   compared   to IUI alone  and also that   the likelihood of pregnancy   is higher  with IUI  than with   timed  intercourses in stimulated  cycles. 

 The dying art !!! Can we revive it  ?? How effective is   IUI  Male   Factor  Subfertility? The road of success of the process of IUI depend five factors but honestly speaking we don’t often follow such in our statistical analysis or counsellling. Such factors which control outcome are   A) density in raw sample, B) density in prepared sample   C) kind of ovarian stimulation, D) Sperm function tests & lastly E) Age of female partner  

Factor I:  The  sperm density and  total sperms per ejaculate : : The success of “Gonadotropins –IUI” in male factor subfertility depends on   sperm density and  total sperms per ejaculate.   The male  sub fertility is a typical indication  for IUI before proceeding to more invasive and expensive    assisted reproductive   technologies such  IVF-ET  or ICSI .  Sadly,    the threshold value   of  raw seminal   parameters  which is     compatible with   an acceptable   outcome of the IUI  treatment   is not univocally defined.  Dickey   et  al in a  large    meta analysis   showed that the efficiency  of IUI   decreased markedly when the sperm concentration was lower   than 5 million per  ml and   the total  sperm  count    lesser  than  10 millions .These are pre process values.  

Factor II : The road to success  of “Gonadotropins –IUI” in male factor subfertility is  post wash sperms density !!! What about Post wash criteria where IUI may be tried?? This   threshold value   was  reported   also in a large   retrospective  cohort study  and more   recent  works  attended   to correlate  the outcome of an IUI  treatment    to the semen  characteristic   evaluated  after   processing the sample . This approach   provides a more standardized   parameter to screen the couples     and to make a proper   counseling   . It is reported  that a number   of total  motile   sperm inseminated lesser   than 5   million /ml  is associated  with a poor   outcome  .Most authors under  these circumstances suggest that the in vitro fecundation could be considered  as  the first  choice  therapy.

Factor III: Gonadotrophin useful?? The road to success  of :”IUI” in male factor subfertility depends on kind of stimulation :  Although    it is generally   thought   that ovarian   stimulation  improves the outcome   of IUI  for male   sub fertility  too , only few randomized  controlled  trials have  investigated  this topic extensively. Long back, a comparative  analysis was   published  in 1991   that concluded that   “ In the  treatment   of male factor   related  infertility  the cycle  fecundity rate    and the cumulative pregnancy rates were   significantly    greater     using a combination   of hMG  and IUI   compared with each modality    alone” . The same  conclusion was  achieved  in a randomized  and longitudinal study   in which the efficiency    of hMG   superovulation plus IUI was compared    to IUI alone in the treatment   of various cases  of infertility  included   the male    related    one. The combination   of IUI and ovulation    induction was showed  to be a more    effective therapy  to enhance    fertility than IUI  alone for   treatment of  both unexplained  and male  related  sterility.

However more recent   studies   demonstrated only a little benefit of adding   superovulation    to IUI in   this category  of patients  and evidenced   in all cases only   a small efficiency in  treating   the male factor  related infertility   with a   non   negligible   number of multiple   pregnancy  . Recently    a Cochrane review  was published  those aim was to  investigate whether   in couples with male subfertility IUI improves  the live   birth rate or ongoing pregnancy     rates compared with timed  intercourse or  vice versa because   of the absence    of large  randomized  controlled   trials.

 A possible   explanation of these different conclusions   and recommendations encountered reviewing  the literature    is probably  connected  to the procedure  used  for to select the couples   candidates to this treatment  program . In fact, most researchers are of  opinion  that  the IUI with superovulation  must be   offered only in case  of mild male  factor excluding  the patients with  moderate or severe oligospermia  and with compromised  morphology .

Factor IV  is CAPACIATION :of sperms (sperm function tests prior to IUI : The milestone in  success of “Gonadotropins –IUI” for  male factor subfertility Some ART specialist even insist on    the execution    of a  capacitation  test on the semen  prior of the   starting   treatment    may provide   a lot of useful information    on the number of   motile sperm available thus excluding   for the therapy patients with    a severe seminal   impairment   defined as  less than 5 million of motile   sperm   recovered.

Factor IV   is age of female partner an important factor which is little discussed while analyzing PR !! We yield to their request for IUI even when the Feale partner is of  age of > 40yrs. . : The success of “Gonadotropins –IUI” in male factor subfertility: Female age is an important factor for outcome Furthermore another critical factor    with an independent prognostic   power seems to be the age of  the female. At this   regard a recent   paper by Bradawl et al  reported   a remarkable   effect of  the maternal age   on the outcome of superovulation   and IUI in this work   no pregnancies occurred above   the female age of 35 years   when less   than 5 million   of motile sperm were inseminated and even when more than 5 millions    of motile  sperm were inseminated the pregnancy   rate was significantly   lower  if compared   to that observed in younger    females The   prognostic    value of the    female   age is also highlighted   in another   large meta analysis. For  this reason some clinicians    suggest    directly  to perform   an in vitro fecundation in the older women.

In summary   we think   that in selected couples with infertility related  to a mild   male factor the superovulation with IUI may be  considered as a first choice   treatment   because it is simple safe and  cost effective.