PCOS and EP

7232019 PCOS and EP

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The association between polycystic ovary syndrome and ectopic pregnancy after in

vitro fertilization and embryo transfer

ARTICLE in AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY middot MAY 2013

Impact Factor 47 middot DOI 101016jajog201305007 middot Source PubMed

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Jing Wang

379 PUBLICATIONS 8739 CITATIONS

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Yongyue Wei

Nanjing Medical University


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Feiyang Diao

Magee-Womens Hospital


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Wei Wang

Huazhong University of Science and Techhellip


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Available from Feiyang DiaoRetrieved on 17 December 2015

7232019 PCOS and EP


REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY

The association between polycystic ovary syndromeand ectopic pregnancy after in vitro fertilization and

embryo transferJing Wang MD Yongyue Wei PhD Feiyang Diao MD PhD Yugui Cui MD PhD Yundong Mao MD PhD

Wei Wang MD Jiayin Liu MD PhD

OBJECTIVE We sought to assess the association between poly-

cystic ovary syndrome (PCOS) and ectopic pregnancy after in vitro

fertilizationeembryo transfer (ET)

STUDY DESIGN In this retrospective cohort study we included 5339

women who had clinical pregnancies after in vitro fertilization treat-

ment (PCOS 205 women non-PCOS 5134 women) at Nanjing

Medical University (China) between 2007 and 2011 Fresh and cryo-

thawed ET cycles were analyzed respectively The primary outcome

measure was the occurrence of ectopic pregnancy Multivariate

logistic regression analysis was used to adjust for important

confounders

RESULTS In fresh ET cycles of women who were undergoing

controlled ovarian hyperstimulation (COH n frac14 3303) women with

PCOS had 306 times higher risk of ectopic pregnancy compared with

those without PCOS (70 vs 24 adjusted odds ratio [aOR] 306

95 confidence interval [CI] 134e696) In the stratified analysis for

women without PCOS the high estradiol group ( gt4085 pgmL) had

higher ectopic pregnancy rates compared with the low estradiol group

( 4085 pgmL 34 vs 20 aOR 199 95 CI 119e335)

however for women with PCOS both high and low estradiol groups

had high ectopic pregnancy rates (56 vs 77 aOR 092 95 CI

015e567) In cryo-thawed ET cycles without COH (n frac14 2036) the

ectopic rates between women with and without PCOS were similar

(22 vs 20 aOR 094 95 CI 022e

407)

CONCLUSION PCOS was associated with an increased risk of ectopic

pregnancy after COH in fresh ET cycles but not in cryo-thawed ET

cycles A possible explanation is that compared with women without

PCOS women with PCOS appear to hold a lower threshold of

hyperphysiologic estradiol level that triggers the occurrence of ectopic

pregnancy after COH

Key words ectopic pregnancy estradiol IVF-ET polycystic ovary

syndrome risk

Cite this article asWang J WeiY Diao F et alThe associationbetween polycystic ovary syndrome andectopic pregnancyafter in vitro fertilization andembryo transfer

Am J Obstet Gynecol 2013209139e1-9

E ctopic pregnancy (EP) is a knowncomplication of in vitro fertilization

(IVF) The reported incidence of EPsafter IVF varies from 21-86 of all

clinical pregnancies12 which is higher

than the estimated EP rate of 197 per100 pregnancies among the general

population in the United States3 and the10 per 100 pregnancies incidence in

China Abnormal estradiol andor pro-gesterone milieu has been proposed as a

risk factor for EP4-6 during IVF treat-

ment hyperphysiologic hormonal levelswhich are associated with controlled

ovarian hyperstimulation (COH) havebeen linked to an increased risk of EP78

Polycystic ovary syndrome (PCOS) isa common disorder that is associated

with infertility in women who undergo

IVF treatment and is characterized by ovulatory dysfunction and endocrine

disorders such as hyperandrogenism9 In

IVF cycles women with PCOS are highly sensitive to medication during COH10

and exhibit possibly higher estradiol

and progesterone levels on the day of

human chorionic gonadotropin (hCG)administration compared with women

without PCOS11 which suggests that

they might be at an increased risk of EPAbundant literature has reported an

increased risk of pregnancy complica-tions in women with PCOS after both

natural conception and assisted re-

productive technologies which includemiscarriage preeclampsia very preterm

birth gestational diabetes mellitus

From the State Key Laboratory of Reproductive Medicine Clinical Center of Reproductive MedicineFirst Af 1047297liated Hospital (Drs J Wang Diao W Wang Liu Cui and Mao) and the Department of Epidemiology and Biostatistics School of Public Health(Dr Wei)Nanjing Medical University NanjingP R China

Received Feb 13 2013 revised April 5 2013 accepted May 1 2013

Supported by research grant number 2012CB944902 from the National 973 Program of China andgrant number 81070465 from the National Natural Science Foundation of China

The authors report no con1047298ict of interest

Presented in part in oral format at the 5th World Congress on Mild Approaches In AssistedReproduction Copenhagen Denmark May 4-6 2012

Reprints Jiayin Liu MD PhD State Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine First Af 1047297liated Hospital Nanjing Medical University 300 Guangzhou RoadNanjing 210029 China jyliu_nj126com

0002-9378$3600 ordf 2013 Mosby Inc All rights reserved httpdxdoiorg101016jajog201305007

AUGUST 2013 American Journal of Obstetrics amp Gynecology 139e1

Research wwwAJOGorg

7232019 PCOS and EP


meconium aspiration and large forgestational age independent of assisted

reproductive technologies12 However

with regard to EP the clear associationbetween PCOS and EP after IVF has not

been reported yet although some studies

mentioned EP rates of women withPCOS who conceived after different

assisted reproductive technologies treat-ment modalities The reported rates are

inconsistent and vary from 0-1013-22

because of different treatment and

grouping methods that have been used

The purpose of this study was to

analyze the possible association betweenPCOS and EP among clinical pregnan-cies that are achieved by fresh and cryo-

thawed IVF cycles If the association

exists we also aimed to assess its possiblecause

MA T E R I A L S A N D METHODS

This study was a retrospective cohort

analysis of women who achieved clinical

pregnancies after IVF-ET in the ClinicalCenter for Reproductive Medicine First

Af 1047297liated Hospital of Nanjing MedicalUniversity between January 2007 and

December 2011 Data for individuals

who started IVF treatment in our clinical

center have been captured routinely in the Database of Clinical Center of

Reproductive Medicine since 2006 Thedatabase includes the detailed infor-

mation on patientsrsquo demographic andbaseline characteristics medical history

infertility-associated disorders such as

PCOS data of IVF procedure andfollow-up pregnancy outcomes With

access to the database with a unique

treatment identi1047297cation number for eachpatient trained nurses collected the pa-

tientrsquos medical and treatment informa-tion continuously along with the IVF

procedure until each embryo transfer

(ET) procedure ended with a follow-uppregnancy outcome

PCOS was diag nosed based on the

Rotterdam criteria23 which means theful1047297lment of 2 of the 3 diagnosis criteria

(presence of oligoovulationanovulation

polycystic ovaries and excess adrogen

activity) and excluding other diseasesthat would represent these

During the study period 15924 ETcycles were performed The overall

implantation rate clinical pregnancy rate and live birth rate were 279

(826329638) 419 (667515924) and

352 (561315924) per ET respec-

tively Of these ET cycles 6675 resultedin pregnancies To ensure no duplication

of data from the same patient who un-derwent multiple treatment cycles only cycles that resulted in the 1047297rst clinicalpregnancy during the study period were

included Because embryo implantation

potential affected EP occurrence1 preg-

nancies that resulted from donated oo-

cytes or sperm were excluded from the

analysis Moreover cycles that involvedpreimplantation genetic diagnosis orin vitro maturation were excluded All

patients who were included were Chi-

nese Fresh and cryo-thawed ET cycleswere analyzed separately For fresh ETcycles to avoid interference by cryo-

preservation cycles with cryopreserved

oocytes or sperm were excluded Addi-tionally to eliminate the bias caused by treatment natural cycles (n frac14 58) and

mild stimulation cycles (n frac14 166) were

excluded from the fresh ET cycles Thus

the 1047297nal study population consisted of 5339 women who achieved clinical

pregnancies These women were group-

ed by diagnosis of PCOS into PCOS andnon-PCOS cohorts in fresh and frozen-thawed cycles respectively

The primary outcome measure was the

occurrence of EP which was diagnosed by

ultrasound examination or laparoscopicsurgery visualizing 1 gestational sacs

outside the uterus or by abnormally

increasing serum hCG level withoutsonographicvisualization and the absenceof chorionic villi inside the uterus after

uterine curettage which was treated by

methotrexate A clinical pregnancy wasde1047297ned as the ultrasound observation of 1 gestational sac at 6 weeks after ET or

diagnosis of an EP A clinical intrauterine

pregnancy was diagnosed as a pregnancy with 1 gestational sacs detected withinthe uterus cavity Heterotopic pregnancy

was de1047297ned when fetal heart beat was

found at both intrauterine and ectopic

sites All EPs were followed until a urinehCG test was negative after treatment In

our study either ectopic or heterotopic

pregnancy was categorized as EP TheEP rate was calculated by dividing EPs

by the total number of clinical pregnan-cies (sum of ectopic and clinical intra-

uterine pregnancies)

In fresh ET cycles all cycles weretreated with COH under which 3

standard regimens applied gonado-

tropin-releasing hormone

e

agonist long protocol (73) gonadotropin-releas-

ing hormoneeagonist short protocol(20) or gonadotropin-releasing hor-

moneeantagonist protocol (7) In

frozen-thawed ET cycles COH wasnot performed instead 3 methods of

endometrial preparation were carried

out that included natural (44) arti1047297-cial (19) and mild stimulation (37)

protocol Mild stimulation refers toovarian stimulation with the use of

clomiphene citrate or letrozole andsubsequently the administration of hu-man menopausal gonadotropin or not

depending on follicle growth Good -

quality embryos were de1047297ned as embryoswith a normal cleavage rate and 10

fragmentation The embryos weretransferred with the Cook Sydney IVF

ET catheter (K-Jets-7019-SIVF Cook

IVF Eight Miles Plains QueenslandAustralia) and placed 15-2 cm below

the fundus under ultrasound guidance

Approval from the institutional re-view board was not required because

our center has been licensed by theMinistry of Public Health of Peoplersquos

Republic of China since 2001 this was a

retrospective study with no speci1047297cclinical intervention on IVF treatment

For univariate analysis of clinical

variables and the outcome measures 2-sample t tests 2-sample Wilcoxon testsc2 or Fisher exact test were used where

appropriate To estimate the indepen-

dent association between PCOS and EPwith the adjustment of important con-

founders multivariate logistic regressionmodels were used Considering differ-

ent features in fresh and frozen-thawed

ET cycles 2 independent regressionmodels were constructed Based on

published 1047297ndings the conf ounding variables included previous EPs24 tubal

factor infertility endometriosis malefactor infertility other infertility factors

number of embryos transferred12

endometrial thickness

25

days of stimu-lation gonadotropins dosage ovarian

Research Reproductive Endocrinology and Infertility wwwAJOGorg

139e2 American Journal of Obstetrics amp Gynecology AUGUST 2013

7232019 PCOS and EP


stimulation protocol78 and estradiol6-8

and progesterone levels on hCG day45

We also performed univariate logistic

regression analysis to select potential EPrisk factors that had a probability value

of 05 from the variables in baseline

and cycle characteristics among the pa-tients who were recruited The EP risk

factors that were distributed unevenly inPCOS and non-PCOS groups were also

included in the logistic regression model

as confounders It turned out that theselected EP risk factors were a subset of

the confounding variables mentioned

earlier The independent risk effect of PCOS on EP was represented by adjusted

odds ratio (OR) and 95 con1047297denceinterval (CI)

To identify a possible explanation onhow PCOS affected EP developmentvariables that were observed as risk fac-

tors for EP were analyzed Joint effect

analysis of PCOS and tubal factor infer-tility in logistic regression model was

performed Estradiol on the day of hCG administration was categorized by

percentile analysis With the use of the

published literature826 estradiol con-

centrations below or above the 75th

percentile (4085 gt4085 pgmL) were

de1047297

ned as the low and high estradiolgroup respectively We strati1047297ed ouranaylsis by having PCOS or non-PCOS

in the logistic regression model to

estimate the possible effect modi1047297cationof the variable on the association be-

tween PCOS and EP

The data were analyzed with theSAS statistical system (version 92 SAS

Institute Inc Cary NC) A probability value of 05 was considered to be

statistically signi1047297cant

R ESULTS

A total of 5339 women who achievedclinical pregnancies were recruited in

this study among whom 123 (23)

had EPsAmong the 5339 women 3303

women conceived after fresh ET and2036 women conceived after frozen-

thawed ET The ectopic rates were

similar in fresh (25 833303 women)and frozen-thawed ET cycles (20

402036 women OR 078 95 CI053e114 P frac14 195) However when

the study population was grouped as

women with and without PCOS theoverall EP rate was signi1047297cantly higher

in women with PCOS (49 10205

women) compared with those withoutPCOS (22 1135134 women OR

228 95 CI 118e

442 P frac14 027)

Fresh ET cycles

The total of 3303 women who achieved

clinical pregnancies after fresh ET weredivided into 2 groups women with

PCOS (n frac14 114) and without PCOS(n frac14 3189)

Table 1 shows the baseline character-istics for women in the 2 studied groups

Women with PCOS were characterizedby fewer previous conceptions and pre-

vious EPs higher body mass index

luteinizing hormone level and lower

follicle-stimulating hormone level Theproportions of infertility factors were

comparable (Table 1) Table 2 showsthe fresh cycle characteristics Cyclefeatures of women with PCOS werecharacterized by more numbers of

previous IVF cycles longer duration

of ovarian stimulation more oocytes

fertilized oocytes cryopreserved em-bryos obtained and more cycles having

surplus embryos cryopreserved Antag-

onist stimulation protocol was used

TABLE 1Baseline characteristics for patients having fresh embryo transfer

VariableWomen withPCOS (n[ 114)

Women withoutPCOS (n[ 3189) P value

Maternal age ya 295 32 300 38 240b

Type of infertility n () lt 001c

Primary infertility 92 (807) 1745 (547)

Secondary infertility 22 (193) 1444 (453)

Parity n () 108c

0 109 (956) 2913 (913)

1 5 (44) 276 (87)

Previous spontaneous abortions n () 906c

0 104 (912) 2899 (909)

1 10 (88) 290 (91)

Previous ectopic pregnancies n () lt 001c

0 109 (956) 2524 (791)

1 5 (44) 665 (209)

Body mass index kgm2a 230 30 217 26 lt 001b

Basal days 2-4 IULa

Follicle-stimulating hormone level 68 15 76 28 lt 001b

Luteinizing hormone level 76 49 44 44 lt 001b

Male factor n () 42 (368) 1445 (453) 074c

Tubal factor n () 40 (351) 1402 (440) 060c

Endometriosis n () 6 (53) 301 (94) 076c

Salpingectomies n () 4 (35) 230 (72) 130c

Other infertility factors n ()e 1 (09) 59 (19) 723d

PCOS polycystic ovary syndrome

a Values are given as mean SD b Two-sample t test c Pearson c2 d Fisher exact test e Other infertility factors infertilityrelated to immunologic factors diminished ovarian reserve maternal chromosome abnormality disorders or other chronicdiseases

Wang Association of PCOS and ectopic pregnancy after IVF-ET Am J Obstet Gynecol 2013

wwwAJOGorg Reproductive Endocrinology and Infertility Research


7232019 PCOS and EP


TABLE 2

Cycle characteristics and ectopic pregnancy outcome in patients having fresh embryo transfer



Year of in vitro fertilization procedures n () 176b

2007 18 (158) 370 (116)

2008 21 (184) 665 (209)

2009 37 (325) 806 (253)

2010 18 (158) 609 (191)

2011 20 (175) 739 (232)

Previous in vitro fertilization cycles na 14 10 12 07 042c

Days of stimulation na 98 28 87 16 lt 001d

Gonadotropins dosage IUa 17369 5842 17338 5450 956d

Ovarian stimulation protocol n () lt 001b

Long protocol 82 (719) 2321 (728)

Short protocol 0 (0) 659 (207)

Antagonist protocol n () 32 (281) 209 (66)

Estradiol on hCG day pgmLa 35281 20259 31858 17594 135c

Progesterone on hCG day ngmL 13 06 14 06 005c

Progesterone estradiol on hCGday 1000 na

048 044 054 037 lt 001c

Endometrial thickness on embryo transfer day mma 112 19 110 21 308d

Oocytes retrieved na 137 56 109 55 lt 001d

Follicles 14 mm on hCG day na 119 53 90 41 lt 001d

Metaphase II oocytes na

126 49 101 48 lt 001d

Fertilized oocytes 2 pronuclear na 90 44 71 37 lt 001d

Fertilization rate a 716 180 718 193 891d

Good-quality embryos rate a 647 283 600 292 066d

Embryo transferred n () 624c

1 14 (123) 230 (72)

2 91 (798) 2822 (885)

3 9 (79) 137 (43)

Day of embryo transfer n () 297e

2-4 113 (991) 3180 (997)

5-6 1 (09) 9 (03)

Cycles with assisted hatching n () 1 (09) 113 (35) 185e

Cryopreserved embryos n ()a 49 34 34 30 lt 001d

Cycles with surplus embryos cryopreserved n () 102 (895) 2445 (767) 001b

Ectopic pregnancy n () 8 (70) 75 (24) 007e

hCG human chorionic gonadotropin PCOS polycystic ovary syndrome

a Values are given as mean SD b Pearson c2 c Two-sample Wilcoxon test d Two-sample t test e Fisher exact test




7232019 PCOS and EP


more commonly for women with PCOSRegarding hormonal pro1047297les on the

day of hCG administration estradiol

concentration was not signi1047297cantly in-creased progesterone concentration was

signi1047297cantly lower and progesterone

estradiol was signi1047297

cantly higher inwomen with PCOS than in women

without PCOS (Table 2)The EP rate in women with PCOS was

signi1047297cantly higher compared with that

in women without PCOS (70 [8114]vs 24 [753189] OR 313 95 CI

147e666 P frac14 007) To assess the in-

dependent impact of PCOS on the risk of EP a multivariate logistic regression

analysis was performed that controlledfor the following important confounders

together with PCOS previous EPs tubalfactor infertility endometriosis malefactor infertility other infertility factors

number of embryo transferred days

of stimulation gonadotropins dosageovarian stimulation protocol estradiol

levelson hCGday progesterone levels onhCG day and endometrial thickness

The results showed that women with

PCOS had a signi1047297cantly higher risk of EP even after adjustment for these con-

founders (adjusted OR 306 95 CI

134e

696 P frac14

008)Among variables in baseline and cycle

characteristics tubal factor infertility and estradiol level on hCG day were

associated signi1047297cantly with EP Women

with tubal factor infertility had a higherrisk of EP compared with women

without tubal factor (adjusted OR 190

95 CI 117e308 P frac14 010) The jointeffect of PCOS and tubal factor infertility

was explored by comparison withwomen without PCOS and tubal factor

which showed a signi1047297

cantly higher jointrisk effect (adjusted OR 457 95 CI126e1657 P frac14 021) In addition

women with both PCOS and tubal factor

tended to have the highest risk of the

development of EP (Table 3)Women in the high estradiol group

had a signi1047297cantly higher risk of EP

compared with those women in the low

estradiol group (35 [29825] vs 22[542478] adjusted OR 183 95 CI

112e301 P frac14 016) Speci1047297cally in the

strati1047297

ed analysis for women withoutPCOS the high estradiol group had

higher EP rates than the low estradiolgroup (34 [27789] vs 20 [482400] adjusted OR 199 95 CI

119e335 P frac14 009) for women with

PCOS high EP rates were observedin both the groups (56 [236] vs 77

[678] adjusted OR 092 95 CI015e567 P frac14 928 Table 4)

Cryo-thawed ET cycles


clinical pregnancies after cryo-thawedET were divided into 2 groups women

with PCOS (nfrac14 91) and women withoutPCOS (n frac14 1945)

Tables 5 and 6 show the baseline and

cycle characteristics for women who

underwent frozen-thawed treatment

Women with PCOS were characterizedby fewer previous conceptions higher

luteinizing hormone level lower follicle-

stimulating hormone level more cry-opreserved embryos and cycles having

surplus embryos cryopreserved Nonatural cryo-thawed ET cycles applied to

women with PCOS Less male factor

infertility occurred in women withPCOS proportions of other infertility

factors were similar

EP rates between women with andwithout PCOS were comparable (22

[291] vs 20 [381945] OR 11395 CI 027e475 P frac14 699) Multivar-

iate logistic regression showed a similar

result (adjusted OR 094 95 CI

022e

407 P frac14

941) after adjustment forprevious EPs endometriosis male factor

infertility tubal factor other infertility factors number of embryo transferred

ovarian stimulation protocol and endo-metrial thickness Women with tubal

factor were also at a higher risk of EP than

women without tubal factor (adjustedOR 259 95 CI 133e504 P frac14 005)

COMMENT

We found that PCOS was associated with

an increased risk of EP after COH in

fresh ET cycles but not in cryo-thawedET cycles Furthermore in fresh ET cy-

cles after COH relatively high EP rateswere observed for only women without

PCOS who had high estradiol levelsHowever for women with PCOS high

EP rates were observed regardless of their

estradiol levelIn our study we analyzed the associa-

tion between PCOS and EP using

matched non-PCOS cohort and adjust-ment for potential confounders Although

the EP rates of women with PCOS werementioned in some studies13-22 their as-

sociation has never been demonstratedBecause different IVF treatment would

bias results we assessed fresh and frozen-

thawed ET cycles separately In fresh ETcycles after COH women who exhibited

high estradiol levels on the day of hCGadministration were found to have a

higher EP risk than those with low

estradiol level This 1047297nding concurs withprevious studies that have reported high

hormonal level after COH as a risk factorfor EP78 and a potential critical role

TABLE 3

Joint effect of PCOS and tubal factor on ectopic pregnancy risk in freshembryo transfer cycles

PCOSTubalfactor

Women (n[ 83)with ectopicpregnancy n ()

Women (n[ 3220)with intrauterinepregnancy n ()

AdjustedOR (95 CI)a P valuea

No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021

CI confidence interval hCG human chorionic gonadotropin OR odds ratio PCOS polycystic ovary syndrome

a Adjusted for previous ectopic pregnancies endometriosis male factor infertility other infertility factors number of embryotransferred days of stimulation gonadotropins dosage ovarian stimulation protocol estradiol levels on hCG day proges-terone levels on hCG day and endometrial thickness




7232019 PCOS and EP


of estradiol on EP development27 No

associations were observed between EP

and progesterone levels or progesteroneestradiol ratio (data not shown) in our

studyIn the strati1047297ed analysis a more

interesting 1047297nding showed that women

with PCOS had high EP rates even un-der a relatively low estradiol level after

COH This 1047297nding is in contrast to the

women without PCOS who had higher

EP rates only when their levels of estra-diol were high (Table 4) We postulatethat women with PCOS hold a lower

threshold for hyperphysiologic estradiol

level which triggers the occurrence of EP This hypothesis provides an expla-

nation for no signi1047297cantly increased

estradiol level in women with PCOS andthe increased risk of EP that was

observed among these women who un-derwent fresh ET cycles

Our data also con1047297rmed the well-

known fact that tubal factor infertility is a risk factor for EP after IVF treat-

ment12 Some women with PCOSamong our cohorts had tubal factor

thus it is natural to conclude that the

impact of PCOS on EP was caused by tubal factor infertility However the

proportion of tubal factor infertility among PCOS and non-PCOS groups

was comparable in fresh and cryo-

thawed ET cycles but the signi1047297cant ef-fect of PCOS on the increased EP risk

was observed only in fresh ET cyclesMoreover we performed a joint effect

analysis on the risk of EP relating to these2 important factors in fresh ET cycles

After adjustment for important con-

founders PCOS and tubal factor bothin1047298uenced the occurrence of EP inde-

pendently (Table 3)Our study has several limitations

First the number of women with PCOS

whose data were analyzed was relatively small In our clinic women with PCOS

accounted for 10 of all patients (data

not shown) among which 38 (2055339 women) were treated with IVF The

reason that IVF treatment accounted fora small proportion of cases was that IVF

is the third-line therapy for ovulation

induction in women with PCOS andpatients are treated with IVF only when

all other treatments have failed to result

in pregnancies Although the limitedsample size precluded us from drawing

solid conclusions to the best of ourknowledge our study is the 1047297rst to focus

on the in1047298

uence of PCOS on EP afterIVF-ET which is just a starting point forfuture study in a large series A second

limitation is that in cryo-thawed ET

cycles the hormonal pro1047297les on theday of hCG administration were not

measured however under the cryo-thawed ET treatments condition the

estradiol level should be close to natural

condition which would be lower thanthat after COH The third limitation is

that because of limited sample size the

effect of different COH protocols onEP could not be analyzed in this study

Finally causes for EP may vary by race or

ethnicity For example smoking was

identi1047297ed as a critical risk factor for EPthe prevalence of smoking is only 03

among Chinese women who are 25-34 years old28 Thus observations from the

Chinese population in this study should

be applied with caution to the hetero-geneous populations Moreover the

limited number of women who smoke

in our study population (n frac14 29) pre-

cluded us from considering smoking asa variableGiven variations in treatment and

grouping methods it is dif 1047297cult to make

a direct comparison on EP rates acrossdifferent studies The overall EP rate

in our study was 23 which falls

within the ranges of reported EP ratesamong clinical pregnancies after assisted

fertilization (21-86)1 Speci1047297callyRajashekar et al14 reported the ectopic

rate of 55 in women (21384) with

PCOS from all kinds of assisted repro-ductive technologies treatment modal-

ities which is similar to the 49 overallectopic rate of women with PCOS in

our study

In baseline and cycle characteristicscompared with PCOS group the non-

PCOS group exhibited higher previousEPs which is a known risk factor for

EP24 Therefore the increased EP ratesthat were observed among the PCOS

group suggested the signi1047297cant effect of

PCOS on EP development Lower meangonadotropins dosage used for women

TABLE 4

Estradiol-stratified ectopic pregnancy risk with and without PCOS in fresh embryo transfer cycles

Variable

Women with PCOS n () Women without PCOS n ()

Women withectopicpregnancy(n[ 8)

Women withintrauterinepregnancy(n[ 106)





Estradiol on hCGday 4085 pgmL

6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009

Estradiol on hCGday gt4085 pgmL

2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)


a Adjusted for previous ectopic pregnancies endometriosis male factor infertility other infertility factors tubal factor number of embryo transferred days of stimulation gonadotropins dosageovarian stimulation protocol progesterone levels on hCG day and endometrial thickness




7232019 PCOS and EP


with PCOS per day was a treatmentstrategy in our center to avoid ovar-

ian hyperstimulation syndrome We

also treated patients who were at risk of ovarian hyperstimulation syndrome

preventively with hydroxyethyl starch

and the incidence of moderate and se-vere ovarian hyperstimulation syndrome

was 197 (653303 women) in ourstudy Although signi1047297cant differences

were shown in ovarian stimulation pro-

tocols between PCOS and non-PCOSgroups multivariate analysis indicated

PCOS itself was associated with EP

independently of confounders that wereadjusted which include ovarian stimu-

lation protocols When the associationof hyperphysiologic estradiol levels and

EP was assessed stimulation protocolswere also accounted for In the futurelarge series are required to analyze the

effect of different stimulation protocols

on the occurrence of EP in women withPCOS

Considering the possible mechanismsbehind the increased risk of EP among

patients with PCOS in the fresh ET cy-

cles vs the frozen-thawed ET cycles2 major discriminators between the cy-

cles should be considered embryo fac-

tors and hormonal milieu Regarding embryo factors the number of day-5

blastocysts and embryos that weretreated with assisted hatching were

distributed evenly between the PCOS

and non-PCOS groups Thus embryostreatments do not seem to be signi1047297cant

contributors

As to hormonal milieu the underlying mechanism of the results discussed earlier

could be explained by the fundamentalrole of estradiol in the regulation of tubal

physiologic processes such as ciliary beatfrequency29 tubal protein secretion30

embryonic motility31 and implantationprocess32 High estradiol levels may pro-

mote tubal implantation through delete-

rious impact on these function27

Published reports have noted highersensitivity to estrogen action in women

with PCOS3334 which may alter tubal

and uterus peristalsis even in the presenceof relatively low hyperphysiologic estra-

diol levels after COH In turn embryos

that migrate into the fallopian tubeswould be unable to be propelled back into

the uterus An in-depth study on the

proposed mechanism is neededIt should be noted that even though

no associations were observed betweenEP and some variables in baseline and

cycle characteristics (such as body mass

index luteinizing hormone level andnumbers of oocytes) we cannot exclude

the possibility that they may play roles in pathophysiologic mechanisms

behind the increased risk of EP among

women with PCOS after COH giventhat these variables were distributed

unevenly in PCOS and non-PCOS pa-tients The potentially impaired oocyte

and embryonic developmental compe-

tence in women with PCOS might alsoplay roles

In conclusion this study indicated

that PCOS was associated with anincreased risk of EP after COH in fresh

ET cycles but not in cryo-thawed ETcycles A possible explanation is that

compared with women without PCOS

women with PCOS appear to hold alower threshold of hyperphysiologic

estradiol level that triggers the occur-

rence of EP after COH The 1047297ndings

suggested that women with PCOS afterCOH need increased surveillance on

TABLE 5

Baseline characteristics for patients having frozen-thawed embryotransfer



Maternal age y

a

302 39 305 41 517

b

Type of infertility n () 020c

Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)

Previous ectopic pregnancies n () 129c

0 78 (857) 1539 (791)

1 13 (143) 406 (209)

Body mass index kgm2a 220 25 216 27 247b

Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c



Other infertility factors n ()d 1 (11) 67 (34) 366e


a Values are given as mean SD b Two-sample t test c Pearson c2 e Fisher exact test d Other infertility factors infertilityrelated to immunologic factors diminished ovarian reserve maternal chromosome abnormality disorders or other chronicdiseases




7232019 PCOS and EP


EP These patients might bene1047297t from

frozen-thawed ET cycles in reduction of

the risk of EP Con1047297rmation of this study in large series is required -

ACKNOWLEDGMENTS

We thank Jing Xu and Chunxiang Wu (NanjingMedical University) for help with manuscriptpreparation We thank Dr Jack Yu Jen Huang(Stanford University) for professional edits onlanguage

REFERENCES

1 Clayton HB Schieve LA Peterson HBJamieson DJ Reynolds MA Wright VC Ectopic

pregnancy risk with assisted reproductivetechnology procedures Obstet Gynecol 2006

107595-6042 Chang HJ Suh CS Ectopic pregnancy afterassisted reproductive technology what are theriskfactorsCurr OpinObstet Gynecol 201022202-73 Centers for Disease Control and Prevention(CDC) Ectopic pregnancy United States 1990-1992 MMWR Morb Mortal Wkly Rep 19954446-84 Paltieli Y Eibschitz I Ziskind G Ohel GSilbermann M Weichselbaum A High proges-terone levels and ciliary dysfunction a possiblecause of ectopic pregnancy J Assist ReprodGenet 200017103-65

Pulkkinen MO Jaakkola UM Low serumprogesterone levels and tubal dysfunction a

possible cause of ectopic pregnancy Am JObstet Gynecol 1989161934-7

6 Hoover RN Hyer M Pfeiffer RM et al Adverse health outcomes in women exposed inutero to diethylstilbestrol N Engl J Med20113651304-147 Fernandez H Coste J Job-Spira NControlled ovarian hyperstimulation as a risk factor for ectopic pregnancy Obstet Gynecol199178656-98 Wu Z Li R Ma Y et al Effect of HCG-dayserum progesterone and oestradiol concentra-tions on pregnancy outcomes in GnRH agonistcycles Reprod Biomed Online 201224511-209 Goodarzi MO Dumesic DA Chazenbalk G

Azziz R Polycystic ovary syndrome etiology

pathogenesis and diagnosis Nat Rev Endo-crinol 20117219-31

TABLE 6

Cycle characteristics and ectopic pregnancy outcome in patients having frozen-thawed embryo transfer




2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)


Ovarian stimulation cycles n () lt 001b

Natural cycle 0 (0) 905 (465)

Artificial cycle 37 (407) 343 (176)

Mild stimulation cycle 54 (593) 697 (358)


Embryos transferred n () 093c

1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)


Thawed embryos na 25 10 22 09 006d

Survived embryos na 22 07 20 06 006d

Cryosurvival rate a 09 02 09 02 421d







7232019 PCOS and EP


10 Delvigne A Demoulin A Smitz J et al Theovarian hyperstimulation syndrome in in-vitrofertilization a Belgian multicentric study I clin-ical and biological features Hum Reprod199381353-6011 Zhong YP Ying Y Wu HT et al Comparisonof endocrine pro1047297le and in vitro fertilizationoutcome in patients with PCOS ovulatory PCO

or normal ovaries Int J Endocrinol 201249280312 Kjerulff LE Sanchez-Ramos L Duffy DPregnancy outcomes in women with polycysticovary syndrome a metaanalysis Am J ObstetGynecol 201120455813 Zhu YM Gao HJ He RH Huang HFResearch on the protocol of limited ovarianstimulation to prevent ovarian hyperstimulationsyndrome Zhonghua Fu Chan Ke Za Zhi200641740-414 Rajashekar L Krishna D Patil M Polycysticovaries and infertility our experience J HumReprod Sci 2008165-7215 Zhao JZ Chen X Wang PY et al Outcome

of pregnancy in women with PCOS treatedby in vitro maturation of immature oocytesZhonghua Fu Chan Ke Za Zhi 200944409-1216 Nahuis MJ Kose N Bayram N et al Long-term outcomes in women with PCOS initiallyrandomized to receive laparoscopic electrocau-tery of the ovaries or ovulation induction with go-nadotrophins Hum Reprod 2011261899-90417 Mehrabian F Eessaei F The laparoscopicovarian electrocautery versus gonadotropintherapy in infertile women with clomiphenecitrate-resistant PCOS a randomized controlledtrial J Pak Med Assoc 201262S42-418 Naether OG Baukloh V Fischer RKowalczyk T Long-term follow-up in 206 infer-tility patients with polycystic ovarian syndromeafter laparoscopic electrocautery of the ovariansurface Hum Reprod 199492342-9

19 Campo S Ovulatory cycles pregnancyoutcome and complications after surgical treat-ment of PCOS Obstet Gynecol Surv 199853297-30820 Calaf Alsina J Ruiz Balda JA RomeuSarrio A et al Ovulationinduction with a startingdose of 50 IU of recombinant follicle stimulatinghormone in WHO group II anovulatory women

the IO-50 study a prospective observationalmulticentre open trial BJOG20031101072-721 Fernandez H Gervaise A Ectopic preg-nancies after infertility treatment modern diag-nosis and therapeutic strategy Hum ReprodUpdate 200410503-1322 Abu Hashim H Ombar O Abd Elaal I In-trauterine insemination versus timed intercoursewith clomiphene citrate in PCOS a randomizedcontrolled trial Acta Obstet Gynecol Scand201190344-5023 Fauser BC Tarlatzis BC Rebar RW et alConsensus on womenrsquos health aspects of polycystic ovary syndrome (PCOS) the

Amsterdam ESHREASRM-Sponsored 3rdPCOS Consensus Workshop Group Fertil Steril20129728-3824 Farquhar CM Ectopic pregnancy Lancet20059485583-9125 Shapiro BS Daneshmand ST Garner FC

Aguirre M Hudson C Thomas S Evidence of impaired endometrial receptivity after ovarianstimulation for in vitro fertilization a prospectiverandomized trial comparing fresh and frozen-thawed embryo transfer in normal respondersFertil Steril 201196344-826 Kyrou D Popovic-Todorovic B Fatemi HMet al Does the estradiol level on the day of hu-man chorionic gonadotrophin administrationhave an impact on pregnancy rates in patientstreated with rec-FSHGnRH antagonist HumReprod 2009242902-9

27 Shao R Feng Y Zou S et al The role of estrogen in the pathophysiology of tubalectopic pregnancy Am J Transl Res 20124269-7828 Giovino GA Mirza SA Samet JM et al

Tobacco use in 3 billion individuals from 16countries an analysis of nationally representa-tive cross-sectional household surveys Lancet

2012380668-7929 Nakahari T Nishimura A Shimamoto Cet al The regulation of ciliary beat frequency byovarian steroids in the guinea pig fallopian tubeinteractions between oestradiol and progester-one Biomed Res 201132321-830 Shao R Egecioglu E Weijdegard B et alDynamic regulation of estrogen receptor-alphaisoform expression in the mouse fallopian tubemechanistic insight into estrogen-dependentproduction and secretion of insulin-like growthfactors Am J Physiol Endocrinol Metab2007293E1430-4231 Parazzini F Oestrogens and progesterone

concentrations and risk of ectopic pregnancyan epidemiological point of view Hum Reprod199611236-832 Wang H Dey SK Roadmap to embryo im-plantation clues from mouse models Nat RevGenet 20067185-9933 Villavicencio A Bacallao K Avellaira CGabler F Fuentes A Vega M Androgen andestrogen receptors and co-regulators levels inendometria from patients with polycysticovarian syndrome with and without endome-trial hyperplasia Gynecol Oncol 2006103307-1434 Leon L Bacallao K Gabler F Romero C

Valladares L Vega M Activities of steroidmetabolic enzymes in secretory endometriafrom untreated women with polycystic ovarysyndrome Steroids 20087388-95


7232019 PCOS and EP


REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY

The association between polycystic ovary syndromeand ectopic pregnancy after in vitro fertilization and

embryo transferJing Wang MD Yongyue Wei PhD Feiyang Diao MD PhD Yugui Cui MD PhD Yundong Mao MD PhD

Wei Wang MD Jiayin Liu MD PhD

OBJECTIVE We sought to assess the association between poly-

cystic ovary syndrome (PCOS) and ectopic pregnancy after in vitro

fertilizationeembryo transfer (ET)

STUDY DESIGN In this retrospective cohort study we included 5339

women who had clinical pregnancies after in vitro fertilization treat-

ment (PCOS 205 women non-PCOS 5134 women) at Nanjing

Medical University (China) between 2007 and 2011 Fresh and cryo-

thawed ET cycles were analyzed respectively The primary outcome

measure was the occurrence of ectopic pregnancy Multivariate

logistic regression analysis was used to adjust for important

confounders

RESULTS In fresh ET cycles of women who were undergoing

controlled ovarian hyperstimulation (COH n frac14 3303) women with

PCOS had 306 times higher risk of ectopic pregnancy compared with

those without PCOS (70 vs 24 adjusted odds ratio [aOR] 306

95 confidence interval [CI] 134e696) In the stratified analysis for

women without PCOS the high estradiol group ( gt4085 pgmL) had

higher ectopic pregnancy rates compared with the low estradiol group

( 4085 pgmL 34 vs 20 aOR 199 95 CI 119e335)

however for women with PCOS both high and low estradiol groups

had high ectopic pregnancy rates (56 vs 77 aOR 092 95 CI

015e567) In cryo-thawed ET cycles without COH (n frac14 2036) the

ectopic rates between women with and without PCOS were similar

(22 vs 20 aOR 094 95 CI 022e

407)

CONCLUSION PCOS was associated with an increased risk of ectopic

pregnancy after COH in fresh ET cycles but not in cryo-thawed ET

cycles A possible explanation is that compared with women without

PCOS women with PCOS appear to hold a lower threshold of

hyperphysiologic estradiol level that triggers the occurrence of ectopic

pregnancy after COH

Key words ectopic pregnancy estradiol IVF-ET polycystic ovary

syndrome risk

Cite this article asWang J WeiY Diao F et alThe associationbetween polycystic ovary syndrome andectopic pregnancyafter in vitro fertilization andembryo transfer

Am J Obstet Gynecol 2013209139e1-9

E ctopic pregnancy (EP) is a knowncomplication of in vitro fertilization

(IVF) The reported incidence of EPsafter IVF varies from 21-86 of all

clinical pregnancies12 which is higher

than the estimated EP rate of 197 per100 pregnancies among the general

population in the United States3 and the10 per 100 pregnancies incidence in

China Abnormal estradiol andor pro-gesterone milieu has been proposed as a

risk factor for EP4-6 during IVF treat-

ment hyperphysiologic hormonal levelswhich are associated with controlled

ovarian hyperstimulation (COH) havebeen linked to an increased risk of EP78

Polycystic ovary syndrome (PCOS) isa common disorder that is associated

with infertility in women who undergo

IVF treatment and is characterized by ovulatory dysfunction and endocrine

disorders such as hyperandrogenism9 In

IVF cycles women with PCOS are highly sensitive to medication during COH10

and exhibit possibly higher estradiol

and progesterone levels on the day of

human chorionic gonadotropin (hCG)administration compared with women

without PCOS11 which suggests that

they might be at an increased risk of EPAbundant literature has reported an

increased risk of pregnancy complica-tions in women with PCOS after both

natural conception and assisted re-

productive technologies which includemiscarriage preeclampsia very preterm

birth gestational diabetes mellitus

From the State Key Laboratory of Reproductive Medicine Clinical Center of Reproductive MedicineFirst Af 1047297liated Hospital (Drs J Wang Diao W Wang Liu Cui and Mao) and the Department of Epidemiology and Biostatistics School of Public Health(Dr Wei)Nanjing Medical University NanjingP R China

Received Feb 13 2013 revised April 5 2013 accepted May 1 2013

Supported by research grant number 2012CB944902 from the National 973 Program of China andgrant number 81070465 from the National Natural Science Foundation of China

The authors report no con1047298ict of interest

Presented in part in oral format at the 5th World Congress on Mild Approaches In AssistedReproduction Copenhagen Denmark May 4-6 2012

Reprints Jiayin Liu MD PhD State Key Laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine First Af 1047297liated Hospital Nanjing Medical University 300 Guangzhou RoadNanjing 210029 China jyliu_nj126com

0002-9378$3600 ordf 2013 Mosby Inc All rights reserved httpdxdoiorg101016jajog201305007


Research wwwAJOGorg

7232019 PCOS and EP







































(826329638) 419 (667515924) and

352 (561315924) per ET respec-




































e






























25




7232019 PCOS and EP






















de1047297




tween PCOS and EP




R ESULTS












228 95 CI 118e

442 P frac14 027)

Fresh ET cycles






















Parity n () 108c

0 109 (956) 2913 (913)

1 5 (44) 276 (87)


0 104 (912) 2899 (909)

1 10 (88) 290 (91)


0 109 (956) 2524 (791)

1 5 (44) 665 (209)


Basal days 2-4 IULa



Male factor n () 42 (368) 1445 (453) 074c

Tubal factor n () 40 (351) 1402 (440) 060c









7232019 PCOS and EP


TABLE 2





2007 18 (158) 370 (116)

2008 21 (184) 665 (209)

2009 37 (325) 806 (253)

2010 18 (158) 609 (191)

2011 20 (175) 739 (232)





Long protocol 82 (719) 2321 (728)






048 044 054 037 lt 001c





126 49 101 48 lt 001d





1 14 (123) 230 (72)

2 91 (798) 2822 (885)

3 9 (79) 137 (43)


2-4 113 (991) 3180 (997)

5-6 1 (09) 9 (03)










7232019 PCOS and EP





















134e

696 P frac14

















strati1047297
























022e

407 P frac14






COMMENT


















TABLE 3


PCOSTubalfactor




No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021






7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP







































(826329638) 419 (667515924) and

352 (561315924) per ET respec-




































e






























25




7232019 PCOS and EP






















de1047297




tween PCOS and EP




R ESULTS












228 95 CI 118e

442 P frac14 027)

Fresh ET cycles






















Parity n () 108c

0 109 (956) 2913 (913)

1 5 (44) 276 (87)


0 104 (912) 2899 (909)

1 10 (88) 290 (91)


0 109 (956) 2524 (791)

1 5 (44) 665 (209)


Basal days 2-4 IULa



Male factor n () 42 (368) 1445 (453) 074c

Tubal factor n () 40 (351) 1402 (440) 060c









7232019 PCOS and EP


TABLE 2





2007 18 (158) 370 (116)

2008 21 (184) 665 (209)

2009 37 (325) 806 (253)

2010 18 (158) 609 (191)

2011 20 (175) 739 (232)





Long protocol 82 (719) 2321 (728)






048 044 054 037 lt 001c





126 49 101 48 lt 001d





1 14 (123) 230 (72)

2 91 (798) 2822 (885)

3 9 (79) 137 (43)


2-4 113 (991) 3180 (997)

5-6 1 (09) 9 (03)










7232019 PCOS and EP





















134e

696 P frac14

















strati1047297
























022e

407 P frac14






COMMENT


















TABLE 3


PCOSTubalfactor




No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021






7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP






















de1047297




tween PCOS and EP




R ESULTS












228 95 CI 118e

442 P frac14 027)

Fresh ET cycles






















Parity n () 108c

0 109 (956) 2913 (913)

1 5 (44) 276 (87)


0 104 (912) 2899 (909)

1 10 (88) 290 (91)


0 109 (956) 2524 (791)

1 5 (44) 665 (209)


Basal days 2-4 IULa



Male factor n () 42 (368) 1445 (453) 074c

Tubal factor n () 40 (351) 1402 (440) 060c









7232019 PCOS and EP


TABLE 2





2007 18 (158) 370 (116)

2008 21 (184) 665 (209)

2009 37 (325) 806 (253)

2010 18 (158) 609 (191)

2011 20 (175) 739 (232)





Long protocol 82 (719) 2321 (728)






048 044 054 037 lt 001c





126 49 101 48 lt 001d





1 14 (123) 230 (72)

2 91 (798) 2822 (885)

3 9 (79) 137 (43)


2-4 113 (991) 3180 (997)

5-6 1 (09) 9 (03)










7232019 PCOS and EP





















134e

696 P frac14

















strati1047297
























022e

407 P frac14






COMMENT


















TABLE 3


PCOSTubalfactor




No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021






7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP


TABLE 2





2007 18 (158) 370 (116)

2008 21 (184) 665 (209)

2009 37 (325) 806 (253)

2010 18 (158) 609 (191)

2011 20 (175) 739 (232)





Long protocol 82 (719) 2321 (728)






048 044 054 037 lt 001c





126 49 101 48 lt 001d





1 14 (123) 230 (72)

2 91 (798) 2822 (885)

3 9 (79) 137 (43)


2-4 113 (991) 3180 (997)

5-6 1 (09) 9 (03)










7232019 PCOS and EP





















134e

696 P frac14

















strati1047297
























022e

407 P frac14






COMMENT


















TABLE 3


PCOSTubalfactor




No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021






7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP





















134e

696 P frac14

















strati1047297
























022e

407 P frac14






COMMENT


















TABLE 3


PCOSTubalfactor




No No 29 (349) 1758 (546) 100 e

Yes No 5 (60) 70 (22) 394 (140e1112) 010

No Yes 46 (554) 1356 (421) 202 (121e337) 007

Yes Yes 3 (36) 36 (11) 457 (126e1657) 021






7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP







































on the in1047298


























our study






TABLE 4


Variable









6 (77) 72 (923) 100 928 48 (20) 2352 (980) 100 009


2 (56) 34 (944) 092 (015e567) 27 (34) 762 (966) 199 (119e335)






7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP
























contributors































TABLE 5




Maternal age y

a

302 39 305 41 517

b


Primary 61 (670) 1062 (546)

Secondary 30 (330) 883 (454)

Parity n () 244c

0 86 (945) 1769 (910)

1 5 (55) 176 (90)


0 80 (879) 1739 (894)

1 11 (121) 206 (106)


0 78 (857) 1539 (791)

1 13 (143) 406 (209)


Basal days 2-4 IULa



Male factor n () 24 (264) 928 (477) lt 001c

Tubal factor n () 35 (385) 881 (453) 200c









7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP





ACKNOWLEDGMENTS


REFERENCES









TABLE 6





2007 4 (44) 80 (41)

2008 10 (110) 234 (120)

2009 23 (253) 423 (217)

2010 28 (308) 525 (270)

2011 26 (286) 683 (351)








1 12 (132) 300 (154)

2 66 (725) 1496 (769)

3 13 (143) 149 (77)


2-4 85 (934) 1859 (956)

5-6 6 (66) 86 (44)











7232019 PCOS and EP















7232019 PCOS and EP















Documents

PCOS and EP