***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To quantitatively assess the impact of follicle size on oocyte maturation , fertilization , and embryo quality . DESIGN Prospect i ve study . SETTING Academic medical center . PATIENT(S ) Couples undergoing ovarian stimulation and in vitro fertilization ( IVF ) .  INTERVENTION(S ) A total of 235 cycles were monitored prospect ively , and 2934 oocytes were collected from five groups of follicle size . Repeated measures multivariate analyses were used to compare the smaller follicle sizes with the lead follicle . MAIN OUTCOME MEASURE(S ) Oocyte maturation , fertilization , and embryo quality . RESULT ( S ) Compared with the lead follicular group ( > 18 mm ) , the odds of a mature oocyte from a 16 to 18 mm size follicle were 37 % and declined progressively with each size . The odds of fertilization of oocytes from follicles 16 to 18 mm in size was 28 % less than the lead group and decreased with each size . The rate of polyspermy with conventional insemination was increased for the smaller follicular groups ( adjusted odds ratio = 2.37 ) . Follicle size did not predict embryo cell number , but embryos from smaller follicles had a statistically significantly higher fragmentation compared with the lead group . CONCLUSION ( S ) The lead follicular group was most likely to have a mature oocyte that was capable of fertilization and best suited for development into a high- quality embryo . The smaller follicles were capable of producing metaphase II oocytes that could fertilize , but at rates approaching only 60 % that of the lead follicular group Background Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity . In the past decades the number of multiple pregnancies has increased . This trend is partly due to the fact that women start family planning at an increased age , but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation ( IUI COH ) . The cumulative pregnancy rate is 40 % , with a 10 % multiple pregnancy rate . This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer ( IVF e SET ) or Modified Natural Cycle IVF ( MNC IVF ) can reduce the number of multiple pregnancy rates , but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility . Secondly , the aim is to perform a cost effective analyses and assess treatment preference of these couples . Methods / Design We plan a multicentre r and omised controlled clinical trial in the Netherl and s comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle ( MNC ) IVF or three cycles with IVF-elective Single Embryo Transfer ( eSET ) plus cryo-cycles within a time frame of 12 months . Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included . Women with anovulatory cycles , severe endometriosis , double sided tubal pathology or serious endocrine illness will be excluded . Our primary outcome is the birth of a healthy singleton . Secondary outcomes are multiple pregnancy , treatment costs , and patient experiences in each treatment arm . The analysis will be performed according tot the intention to treat principle . We will test for non-inferiority of the three arms with respect to live birth . As we accept a 12.5 % loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies , we need 200 couples per arm ( 600 couples in total ) . Discussion Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications . Should patients find the most cost-effective treatment acceptable or even preferable , this could imply the need for a world wide shift in the primary treatment . Trial registration Current Controlled Trials IS RCT N OBJECTIVE To compare the outcome of natural with clomiphene citrate (CC)-stimulated cycles in IVF . DESIGN Prospect i ve , r and omized study . SETTING Tertiary referral center for assisted conception . SUBJECTS Thirty patients r and omized to receive either no treatment ( n = 14 ) or CC , 100 mg , from days 2 to 6 ( n = 16 ) . INTERVENTIONS Daily ultrasound ( US ) scan and measurements of serum LH and E2 . Ovarian morphology was assessed on baseline US scan . Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm . Transvaginal US-directed oocyte recovery was performed 35 hours later . MAIN OUTCOME MEASURES The number of patients reaching oocyte recovery ; numbers of oocytes collected , fertilized and embryos transferred ; and clinical pregnancy and multiple pregnancy rates ( PRs ) were recorded . RESULTS Ten cycles in the natural cycle group were ab and oned before oocyte recovery compared with none in the CC group . There were significantly more follicles > 14 mm ( 2.4 + /- 0.3 [ SE ] compared with 0.9 + /- 0.2 ) and higher peak levels of E2 ( 375 + /- 67 pg/mL ( 1,378 + /- 247 pmol/L ) compared with 204 + /- 17 pg/mL ( 748 + /- 61 pmol/L ) ) in those receiving CC compared with those receiving no drug . All 16 patients treated with CC had oocyte retrieval ( mean , 1.8 + /- 0.3 oocytes ) compared with only 4 in the natural cycle group ( 1 oocyte each ) . The oocyte recovery rate was 95 % . Two patients conceived in the CC group ( PR per ET , 18 % ) compared with none in the natural cycle group . Patients with polycystic ovaries  developed more large follicles than those with normal ovaries . No patient developed ovarian hyperstimulation syndrome . CONCLUSIONS Patients undergoing natural cycle IVF are more likely to have ab and oned cycles , produce fewer follicles and oocytes , and are less likely to reach ET than patients treated with CC alone . Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired It has been speculated that controlled ovarian hyperstimulation ( COH ) , as performed during in vitro fertilization therapy , may negatively affect embryo  implantation . The objective of this prospect i ve and r and omized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles ( d 21 ) . Analysis was performed with high-density oligonucleotide microarrays . In addition , other structural and functional features of the endometrium were investigated . Results corroborated that  COH  cycles depicted advancement of pinopodes appearance , histological features , and steroid receptor down-regulation when compared with natural cycles . These changes were associated with significant , albeit small , variations in gene expression ( 18 genes/expressed sequence tags and -1.55- to + 3.40-fold changes ) . Second , there were significant changes in gene expression when comparing cycles using a GnRH agonist vs. a GnRH antagonist ( 13 genes/expressed sequence tags and + 1.42- to + 2.10-fold changes ) . This is the first attempt to eluci date gene expression profiles of the endometrium during COH cycles . The observed differences in gene expression in  COH cycles using state-of-the-art protocol s may not have a major functional impact on embryo implantation Background Frozen thawed embryo transfer ( FET ) is a cost- effective adjunct to IVF or IVF-ICSI treatment . In order to optimize treatment outcome , FET should be carried out during a period of optimal endometrial receptivity . To optimize implantation several methods for endometrium preparation have been proposed . In natural cycle FET ( NC-FET ) , the endometrium develops under endogenous hormonal stimulation . The development of the dominant follicle and endometrium is monitored by ultrasound and FET is timed after triggering ovulation induction or determination of the spontaneous LH surge . In an artificial cycle FET ( AC-FET ) estrogens and progesterone are administered to prepare the endometrium for implantation . While the currently available data show no significant difference in pregnancy rates between these methods , well design ed r and omized controlled trials are lacking . Moreover there is little literature on difference in cancellation rates , cost-efficiency and adverse events . Methods and design In this r and omized , multi-centre , non-inferiority trial we aim to test the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET versus AC-FET .  The primary outcome will be live birth rate per embryo transfer procedure . Secondary outcomes will be ongoing and clinical pregnancy rate , cancellation rate , ( serious ) adverse events and cost-efficiency . Based on a live birth rate of 20 % and a minimal clinical important difference of 7,5 % ( one-sided alpha 2,5 % , beta 20 % ) a total of 1150 patients will be needed . Analyzes will be performed using both per protocol as well as intention to treat analyses . Discussion This prospect i ve , r and omized , non –inferiority trial aims to address the hypothesis that there is no significant difference in live birth rates between patients undergoing NC-FET  versus patients undergoing AC-FET .  Moreover it addresses cost-efficiency as well as the perceived burden of both treatments . Trial registerNetherl and s trial register ( NTR ) : To compare oocyte quality and clinical outcome after an ultrashort or a modified suppression gonadotrophin-releasing hormone agonist ( GnRHa ) protocol for ovarian stimulation in intracytoplasmic sperm injection ( ICSI ) cycles , we conducted a prospect i ve r and omized study of 60 consecutive couples with severe male infertility admitted for their first in-vitro fertilization ( IVF ) and ICSI attempt . More cycles were cancelled after the ultrashort protocol ( 8/30 ) than after the modified suppression protocol ( 3/30 ) , although the difference was not significant . There were no cases of severe ovarian hyperstimulation syndrome ( OHSS ) in the ultrashort group compared to three cases in the suppression group . The percentage of mature metaphase II oocytes recovered in both groups was similar ( 88 versus 86 % ) , as were the fertilization or cleavage rates after ICSI . In the ultrashort group , a total of 64 embryos was replaced in 22 transfers ( mean 2.9 embryos per transfer ) , result ing in three first trimester abortions and seven deliveries . In the suppression group , 11 deliveries were achieved after transfer of a total of 75 embryos in 27 patients ( mean 2.8 embryos per transfer ) . In conclusion , there was no apparent difference between the two GnRHa protocol s in terms of oocyte quality and clinical outcome . However , because of the lower rate of severe OHSS , in our study the ultrashort protocol was more appropriate for ovarian stimulation in ICSI cycles than the modified suppression protocol The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only . A total of 132 couples with no previous IVF attempts , selected by female age < 35 years , indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were r and omized to the two protocol s. R and omization yielded two comparable groups . The clomiphene group ( 68 couples ) performed significantly better than the unstimulated group ( 64 couples ) in terms of number of cycles with oocyte harvest ( 90/111 or 81 % versus 65/114 or 57 % ; chi(2 ) = 9.21 , P < 0.002 ) , embryo transfers per started cycle ( 59/111 or 53 % versus 29/114 or 25 % ; chi(2 ) = 18.14 , P < 0.0001 ) , live intrauterine pregnancy rate per started cycle ( 20/111 or 18 % versus 4/114 or 4 % ; chi(2 ) = 12.42 , P < 0.0001 ) , live intrauterine pregnancy rate per embryo transfer ( 20/59 or 34 % versus 4/29 or 14 % ; chi(2 ) = 3.96 , P = 0.047 ) , but not in terms of implantation rate ( 22/85 or 26 % versus 4/29 or 14 % ; chi(2 ) = 1.65 ) . Only two twin pregnancies occurred . Modest side-effects were recorded following clomiphene . Accordingly , a simple clomiphene citrate protocol , but not IVF in unstimulated cycles , seems compatible with the concept of ' friendly IVF ' , yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients . The results do not substantiate any important negative anti-oestrogenic effects of clomiphene OBJECTIVE To determine the efficacy of natural-cycle IVF compared with controlled ovarian hyperstimulation in poor responders . DESIGN R and omized , controlled study . SETTING Private center for assisted reproduction . PATI 
    Output:
    
There were insufficient data to draw any conclusions about rates of treatment cancellation .
Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model : for these outcomes , use of a fixed effect model suggested a benefit for the st and ard IVF group .