the latest advances in ultrasonic measurement techniques have helped indentify that 20~30% women have polycystic ovaries ( pco ) .
the incidence of pco is up to 34% for those women diagnosed by reproductive specialists .
a subpopulation of these pco cases is ovulatory pco , in which women do not display any typical symptom of the polycystic ovary syndrome ( pcos ) although they do have pco .
some ovulatory pco patients reportedly show mild endocrine abnormalities including high levels of luteinizing hormone ( lh ) or androgen as well as insulin resistance , which are similar to those experienced by pcos patients [ 46 ] .
however , a recent study demonstrates that isolated pco is an age - dependent , normal finding among ovulatory women that has no pathologic or clinical significance . to date
, numerous studies have extensively investigated the in vitro fertilization and embryo transfer ( ivf - et ) in pcos patients [ 813 ] , whereas little information is available for ivf - et in ovulatory pco patients [ 1417 ] .
the aim of the present study was to directly address this deficiency in the literature and compare the ovulation and treatment of ivf - et among patients suffering from pcos , ovulatory pco , or normal ovaries with other complications ( no ) .
patients receiving ivf or intracytoplasmic sperm injection ( icsi ) treatment at the reproductive medicine center of the first affiliated hospital , sun yat - sen university , between january and september 2010 , were selected for analysis .
patient information was documented in details , including age , weight , menstruation history , pelvic ultrasound examination results , and basal hormone levels .
patients with endometriosis or any other endocrine complications such as thyroid dysfunction , hyperprolactinemia , cushing syndrome , or atypical congenital adrenal hyperplasia were excluded from the study . based on the diagnosis ,
patients were divided into three groups : pcos ( 122 patients , 122 cycles ) , ovulatory pco ( 208 patients , 208 cycles ) , and normal ovaries ( 660 patients , 660 cycles ) .
there were 122 pcos patients diagnosed according to the rotterdam standard who had a total of 122 ivf / icsi cycles , oligo - ovulation was defined as a menstrual cycle of longer than 35 days ; hyperandrogenism was diagnosed with either clinical or biochemical profiles ; pco was defined as the presence of 12 or more follicles in each ovary measuring 29  mm in diameter , or increased ovarian volume larger than 10  ml .
moreover , 208 ovulatory pco patients had 208 ivf / icsi cycles , which were diagnosed with a regular menstrual cycle ( 2135 days ) , no clinical or biochemical profiles of hyperandrogenism and the presence of 12 or more follicles with a diameter of 29  mm in either side of the ovary , and/or total ovary volume 10  ml .
in addition , 660 patients with normal ovaries had a total of 660 ivf / icsi cycles were recruited as controls , they all exhibited normal ovarian morphology and regular menstrual cycles .
causes of infertility for these patients include tubal blockage , pelvic adhesions , and/or male factor .
. briefly stated , long - acting gonadotropin - releasing hormone agonist 1.0  mg or 1.3  mg was intramuscularly administered in the midluteal phase ( gnrh - a , diphereline , france ) .
following pituitary downregulation , patients were administered gonadotropin ( gn , gonal - f , switzerland ) from the 3th-5th day of the menstrual cycle . the initial gn dose was determined by a variety of factors , including age , number of ovarian follicles , basal fsh levels , and history of ovarian response . during the ovarian stimulation , transvaginal ultrasound and serum sex hormone levels were monitored to evaluate the development of ovarian follicles , and the gn dose was adjusted based on the intensity of ovarian response . when more than ( and including ) 2 ovarian follicles with the diameter 18  mm , or more than ( and including ) 3 ovarian follicles with the diameter 17  mm , were detected , patients were injected with 10,000  iu human chorionic gonadotropin ( hcg , switzerland ) to trigger oocyte maturation .
oocytes were collected about 36 hours later . the fertilization protocol ( regular ivf or icsi )
was determined by the condition of semen on the same day as the oocyte extraction .
embryo transplantation was determined by the number of oocytes , the estradiol ( e2 ) level , and the patient conditions .
no more than three embryos were implanted into the uterine cavity three days after the oocyte extraction .
if the hcg test was positive , ultrasonic examination was conducted two weeks later to determine the clinical pregnancy .
a blood test was performed on the 2nd-5th day of the menstrual cycle before the treatment to determine the levels of fsh , lh , e2 , and testosterone ( t ) .
the pcos and ovulatory pco patients received transvaginal ultrasound before the ivf treatment to examine the pelvic conditions .
all ovulatory pco patients and some of the pcos patients exhibited the symptoms of polycystic ovary . during treatment , patient information was documented , including age , body mass index ( bmi ) , duration of gn administration , total gn dose , e2 levels on the hcg day , endometrial thickness on the hcg day , numbers of collected oocytes , fertilization rates , oocyte cleavage rates , numbers of available embryos and transferred embryos , hcg positive rates , numbers of gestational sacs , incidence of spontaneous abortion , incidence of ovarian hyperstimulation syndrome ( ohss ) , and incidence of cycle cancellation .
the ohss classification was based on the  expert consensus on diagnosis and treatment of polycystic ovarian syndrome  standard set by the endocrinology group of the obstetrics and gynecology society , chinese medical association ( cma ) .
the group differences were analyzed by analysis of variance ( anova ) or rank test for quantitative data and chi - square test for qualitative data .
compared to the no patients , patients with pcos or ovulatory pco were younger ( p < 0.01 ) .
the pcos patients exhibited the highest bmi as well as basal lh and t levels ( p < 0.01 ) , whereas the no patients exhibited the highest basal fsh levels ( p < 0.01 ) ( table 1 ) .
compared to the no patients , patients with pcos or ovulatory pco exhibited a significantly shorter stimulation duration and lower gn dose but showed much higher e2 levels on the hcg treatment day and more achieved oocytes ( p < 0.01 ) ( table 2 ) .
the fertilization rate of the pcos patients was significantly lower than the other two groups .
the pcos and ovulatory pco patients exhibited similar lower cleavage rates , but more available embryos .
we did not observe any significant differences in the numbers of transplanted embryos , pregnancy rates , clinical pregnancy rates , or implantation rates among the three groups .
the pcos patients exhibited a higher miscarriage rate ( 17.5% ) , although the difference was not significant .
the incidence of moderate to severe ohss was 15.8% and 11.1% for the pcos and ovulatory pco patients , respectively , which was significantly higher than that of the no patients ( 5.4% , p < 0.01 ) ( table 3 ) .
besides moderate to severe ohss , cycle cancellation was also a notable adverse outcome of the ivf treatment .
cycle cancellation could be classified into three types : ( 1 ) the cycle was canceled during the process of ovarian stimulation because of poor ovarian response ; ( 2 ) the embryo transfer was canceled due to excessive numbers of oocyte achieved , high e2 levels on the hcg treatment day , and/or showing symptoms of overstimulation , including abdominal distension and apparent pelvic fluid ; ( 3 ) other complications , including oocyte collection failure , abnormalities in the oocyte fertilization and/or cleavage , poor embryo quality , and/or endometrial factors . in the pcos , ovulatory pco , and no patients , the rates of cycle cancellation due to poor ovarian response were 1.6% ( 2/122 ) , 0% ( 0/208 ) , and 2.7% ( 16/660 ) , respectively ; the rates of embryo transfer cancellation were 18.0% ( 22/122 ) , 22.1% ( 46/208 ) , and 4.9% ( 32/660 ) , respectively ; the rates of other causes were 1.6% ( 2/122 ) , 1.0% ( 2/208 ) , and 2.4% ( 16/660 ) , respectively .
thus , the overall rates of cycle cancellation for these three groups were 21.2% ( 26/122 ) , 23.1% ( 48/208 ) , and 10.0% ( 64/660 ) , respectively .
our results suggested that compared to the no patients , the pcos and ovulatory pco patients exhibited significantly higher rates of embryo transfer cancellation and overall cycle cancellation ( p < 0.05 ) .
contrary to some reports [ 46 ] , in the current study , we found that bmi and levels of lh and androgen were similar between the ovulatory pco and no patients , which were significantly higher than those in the pcos patients .
insulin - sensitizing agent metformin which has been examined as a cotreatment during ivf in women with pcos , brought an increase in pregnancy rate   and a significant reduction in rates of ohss , however , for women with pco but no other manifestations of pcos , metformin cotreatment before and during ivf did not bring any positive effect in clinical pregnancy , live birth , or severe ohss .
the most likely explanation is that women with pco may be less insulin resistance compared with women with pcos .
while some women with pco to share some endocrinological abnormalities with those with pcos , the difference between these studies may be attributed to variations in categorizing patients . according to the widely used rotterdam diagnostic criteria for pcos ,
thus , pco and pcos are not necessarily related to each other . in this study
, the ovulatory pco patients did not have the endocrine and metabolic abnormalities manifested by the pcos patients , indicating that polycystic ovary might only represent some normal variation in the ovarian morphology .
all patients in the present study were treated with standard protocol of long - term gnrh - a administration in midluteal phase , which was commonly used for infertility women including pcos patients .
in addition to its well - known advantages such as easy to operate and satisfactory pregnancy rates , for pcos patients , gnrh - a can effectively reduce the lh / androgen level and inhibit the inflammatory factors , thus may improve the quality of the oocytes and embryos as well as endometrial receptivity .
compared with the pcos patients treated with oral contraceptive pill [ ocp ] alone , patients treated with ocp plus long - term gnrh agonist exhibit lower hormone levels and better amelioration of clinical symptoms [ 810 ] .
in addition , the fertilization rates and pregnancy rates of gnrh - a - treated pco patients were similar to those of the non - pco patients .
therefore , based on the current findings , clinical experience , as well as our findings in the present study , we propose that gnrh - a long - term protocol is suitable strategy for the pcos patients treated with ivf .
our study showed that both the ovulatory pco and pcos patients displayed high - ovarian responsiveness , which was consistent with previous research .
compared to the no patients , the ovulatory pco and pcos patients exhibited reduced duration of ovarian stimulation and total gn dose , as well as increased e2 levels and number of collected oocytes .
previous studies have suggested that compared to other infertility patients , pcos patients exhibited a higher degree of ovary vascularization during the process of ovarian stimulation , which paralleled with vascular endothelial growth factor [ vegf ] levels in the serum and follicular fluid .
the ovary vascularization and vegf levels were positively correlated with the e2 levels and numbers of oocytes achieved [ 11 , 22 ] .
coffler et al .   suggest that in pcos patients , follicular granulosa cells can show two types of response to fsh : ( 1 ) pcos patients show remarkably higher e2 levels in response to fsh above the threshold dose ; ( 2 ) pcos patients treated with a single fsh stimulation exhibit much faster rise and decay of the e2 levels , which were much different from the response of the control patients .
however , serum fsh levels of both groups were similar , a phenomenon which is probably explained by the fact that most follicular granulosa cells have either apoptosed or can not effectively respond to fsh .
based on previous and current findings , we conclude that both pcos and ovulatory pco patients are sensitive to gn stimulation , thus it is difficult to determine an appropriate gn dose for each individual patient . in our study , although we gradually reduced the gn dose to avoid such overstimulation , the follicle degeneration and atresia were still observed in some patients , which were also reported by coffler et al . .
compared to the no patients , the pcos but not the ovulatory pco patients showed lower fertilization rates , whereas both groups exhibited a significantly lower oocyte cleavage rates and more available embryos .
thus , we further investigated whether the lower fertilization rates of the pcos patients were due to abnormal oocyte morphology or changes in cytosolic factors which could affect the quality of the oocytes .
previous studies report that the morphology of the cytoplasm and extra cellular matrix of the oocytes and embryos were similar among the pcos , pco , and no patients , indicating that the affected fertilization and early embryonic development of the pcos and/or pco patients are not because of intrinsic abnormalities of the oocytes .
endocrine disorders and internal oocyte abnormalities can also result in low rates of oocyte fertilization and cleavage .
for instance , high lh levels and insulin resistance can cause the malfunction of follicular granulosa cells and the abnormal expression of gdf-9 , both of which markedly reduce the quality of the embryos [ 3 , 14 , 25 ] .
our results also demonstrated that the ovulatory pco and pcos patients exhibited similar rates of pregnancy , clinical pregnancy , and implantation .
although the higher average age of the no patients might be a confounding factor for the analysis , we still considered that the pregnancy rates of the ovulatory pco and pcos patients were satisfactory .
our observations were consistent with previous studies by esmailzadeh et al . , kim et al . , swanton et al . , and esinler et al . .
in esmailzadeh et al . , the fertilization and pregnancy rates of the ovulatory pco patients treated with gnrh - a long - term protocol were similar to those of the non - pco patients .
similar outcomes ( duration of stimulation , dose of gn used , e2 level on hcg day , number of retrieved oocytes , rates of implantation , clinical pregnancy and miscarriage , any incidence of severe ohss ) were observed in patients with pcos and sonographic pco - only for ivf - et treatment .
live birth rates are similar among women with pco ( 38% ) , pcos ( 37% ) , and normal ovaries ( 40% ) .
severe ohss rates were significantly higher in women with pco ( 12.6% ) and pcos ( 15.4% ) compared to those with normal ovaries ( 2.7% ) . in the study of esinler et al . , the satisfactory pregnancy rates of the ovulatory pco and pcos patients were due to sufficient numbers of collected oocytes , fertilized oocytes , and transferred high - quality embryos .
pcos patients exhibited the highest abortion rate , although no significant difference was detected , which could be explained by small sample size and age variation . whether this high risk of abortion is related to the quality of the oocytes
remains unclear . the risk may as well be caused by other factors than the oocytes .
for instance , central obesity patients exhibit high lh levels and insulin resistance which can cause abortion , whereas administration of gnrh - a to these patients can effectively reduce the risk of abortion .
wang et al .   postulated that the relatively high abortion rates in the pcos patients were due to combined effects of obesity , treatment for infertility , and causes of infertility .
after correction for these factors , the abortion rates in the pcos patients were comparable to those in the controls , indicating that the intrinsic factors of pcos contributed little to the abortion issue .
in addition , the high e2 levels induced by ovary stimulation might increase the risk for abortion by lowering the endometrial capacity .
however , both the viewpoints need further research for verification . in summary , a subpopulation of polycystic ovaries cases are called ovulatory pco patients , who do not display high levels of androgen and have regular menstrual cycles although they do have pco . unlike the pcos patients , they have almost normal endocrine and metabolic characteristics and their pco may be a normal variation of ovary morphology . when treated with ivf - et , ovulatory
pco and pcos patients similarly manifest high ovarian responsiveness , relatively good ivf pregnancy rates , and incidence of adverse outcomes , including high ohss risk , cycle cancellation rates and abortion rates ( although the differences were not statistically significant ) .
 
 aim . to compare the basic endocrine profile and outcomes of in vitro fertilization ( ivf ) in women with polycystic ovary syndrome ( pcos ) , ovulatory polycystic ovaries ( pco ) , or normal ovaries ( no ) 
 . methods . the basic clinical features and in vitro fertilization and embryo transfer outcome in patients receiving ivf or intracytoplasmic sperm injection ( icsi ) were retrospectively analyzed . 
 results . 
 the body mass index , basal luteinizing hormone , and testosterone levels were significantly lower in patients with ovulatory pco compared to those in patients with pcos . 
 the pcos patients exhibited the shortest duration of ovarian stimulation and lowest dose of gonadotropin , followed by the ovulatory pco and no patients . 
 the ovulatory pco and pcos patients showed similar levels of e2 on the human chorionic gonadotropin treatment day and numbers of oocytes , which were both significantly higher than those of the no patients . 
 the fertilization rate of the pcos patients was significantly lower than the other two groups . compared to no patients , the cleavage rate was lower in both pcos and ovulatory pco patients , however , the number of available embryos was significantly more in these two groups . 
 the incidence of the moderate to severe ovarian hyperstimulation syndrome ( ohss ) was markedly higher in the pcos and ovulatory pco patients . 
 conclusion . 
 ovulatory pco patients do not express similar endocrine abnormalities as pcos patients . 
 although the fertilization rate and cleavage rate were relatively low in pcos patients , ultimately , all the three groups showed similar transferred embryo numbers , clinical pregnancy rates , and implantation rates . 
 since the incidence of ohss was much higher in the pcos and ovulatory pco patients , we should take more care of these patients and try to prevent severe ohss . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion