Hum. Reprod. Advance Access originally published online on June 22, 2006
Human Reproduction 2006 21(10):2617-2627; doi:10.1093/humrep/del236
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Evidence of improving quality of reporting of randomized controlled trials in subfertility
Biostatistics Group, University of Manchester, Manchester, UK
1 To whom correspondence should be addressed at: Biostatistics Group, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. E-mail: sofia.dias{at}manchester.ac.uk
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Abstract |
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 Top Abstract IntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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BACKGROUND: The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. Our aim was to assess whether this quality has improved over time, particularly since the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement, and to assess what proportion of trials could be included in the meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews. METHODS: A selection of subfertility trials published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. Only trials published in English as full journal articles, claiming to be randomized and reporting on pregnancy outcomes, were included. RESULTS: One hundred and sixty-four trials met our inclusion criteria. Twenty-four (15%) were found not to be randomized, despite claims, and only 10 trials (6%) provided adequate details on the methods of randomization and allocation concealment. Of these, only three had sufficient details extractable to allow for an intention-to-treat analysis of the outcome ‘live birth’. CONCLUSIONS: Although an improvement in some subfertility-specific issues was observed, the quality of reporting of RCTs still needs to improve to make them suitable for inclusion in meta-analyses such as those in the Cochrane Library.
Key words: methodological quality/statistics/subfertility/systematic review
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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The Consolidated Standards of Reporting Trials (CONSORT) statement (Begg et al., 1996
) was published in response to perceived bad quality of reporting of randomized controlled trials (RCTs) (Schulz et al., 1995) and revised in 2001 (Altman et al., 2001; Moher et al., 2001b). Concealed randomization of patients to groups and analysis of the data based on the ‘intention-to-treat’ (ITT) principle are cornerstone recommendations. Recent analysis has demonstrated that despite improvements, poor reporting persisted in 2000 in PubMed indexed trials (Chan and Altman, 2005) and in 2001 in the leading subfertility journals (Vail and Gardener, 2003). The latter review was limited to the two main subspecialty journals, which may publish better quality papers, and focused on a single year, therefore providing no information on how quality might have changed over time. Systematic reviews of the evidence from RCTs usually include a formal statistical summary, or ‘meta-analysis’ of the data retrieved from the original trial publications. For patients involved in fertility studies, the outcome of chief interest is birth itself, rather than an intermediate step in the fertilization process. For this reason, only trials that report pregnancy outcomes for all women were analysed. Even if a trial is otherwise of good quality, poor reporting and presentation of data—to which fertility trials may be especially prone—may mean that the trial has to be excluded.
In addition to general concerns in common with other areas of research, there are particular features of subfertility data that, if not accounted for properly in design and analysis, generate statistical errors that, in turn, may lead to inappropriate conclusions (Daya, 2003). Four areas are of specific concern:
- Repeated cycles have been used to define ‘treatment periods’ for crossover studies in which participants are initially allocated at random but then follow a defined sequence of interventions, often alternating between treatments, until the success or the end of study. There has been ongoing debate in the subfertility literature regarding the use of such designs (Daya, 1993; Cohlen et al., 2004; Norman and Daya, 2004), including contradicting claims of how valid analyses can be obtained (Eijckemans et al., 2002; McDonnell et al., 2004). However, there is agreement in the statistical literature that data from a crossover design cannot provide valid inferences using standard statistical tests, when a participant’s outcome in one period affects participation in subsequent periods (Senn, 1993). When a crossover design is used, only first-stage data (before crossover) are suitable for inclusion in meta-analyses with parallel group studies and these should be clearly presented.
- Randomization should be performed at the latest possible stage before the study intervention is administered, so as to minimize possible dropouts or exclusions. Often in subfertility trials, a sequence of therapies or interventions is given before the study intervention. Failure to respond satisfactorily at preliminary stages will mean that the study intervention cannot be administered but, if already randomized, the patient should still be included in the report of results. Ideally, for trials of subsequent interventions, only patients who have responded to the preliminary interventions should be randomized, e.g. if the intervention is the number of embryos to transfer, only consenting patients who reach the transfer stage (after a number of pre-randomization treatments not relevant to the intervention) should be randomized. In any case, the timing of randomization and reason for exclusions should be clearly reported.
- Subfertility data are generally hierarchical in nature. For each woman, the data can have a tree-like structure: there may be multiple cycles, within each of which there are multiple embryos, arising from multiple oocytes. Typical definitions of pregnancy, fertilization and implantation rates, per cycle, per oocyte or per embryo, respectively, treat two observations in one woman as equivalent to one observation in each of two women. Although information on these rates may be of some interest, standard methods of statistical analysis, based on the assumptions of independence between observations, do not apply to such data because multiple observations on the same woman are likely to be correlated.
- There are multiple stages of subfertility outcome from failure of stimulation through to live birth, via successful fertilization and culture of high-quality embryos, implantation and then biological, clinical and ‘ongoing’ pregnancy. Ultimate success depends on progressing through each previous stage. Trials often report comparisons not of the randomized groups, but of subgroups of participants who have attained intermediate stages, such as ‘per embryo transfer’. The number of women actually randomized to each treatment group who are involved at each intermediate stage is often not extractable, particularly for adverse event reporting.
The aim of this review was to assess the extent of the problem of poor methodological quality and reporting in published RCTs in subfertility and what proportion of trials can be included in meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews. We were also interested in whether quality has improved since the publication of the CONSORT guidelines in 1996. Methodological aspects specific to subfertility and allowing ideal meta-analyses are of special interest.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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A selection of subfertility trials was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. The database includes all mentions of studies and RCTs in subfertility, published in several journals and Conference Proceedings (US Cochrane Center, 2004). On 1 December 2004, 3455 references were available. The earliest available records were published in 1966 (three references), and the database was complete up to 2003. For practical reasons, we chose to remove all trials not published in English and to discard those references not published as full journal articles (such as abstracts from conferences and letters), because the description of methodology is necessarily restricted in such publications. After removing all such references, 1903 records remained for analysis.
We decided to review all trials in the database that purported to be randomized and reported on any form of pregnancy (even if not as the main outcome). We restricted our analysis to trials published in the years 1990, 1996 and 2002 to assess any changes in quality over time, and in particular to capture any differences in quality before the publication of CONSORT (1990 and 1996) and after the CONSORT guidelines had been available for sufficiently long for their impact to be noticeable (2002). Two hundred and sixty-three references were available for these years, all of which were retrieved and checked for eligibility. Ninety-nine references did not satisfy our inclusion criteria and were excluded: 5 references (5%) did not correspond to clinical trials (e.g. literature reviews and case studies); 44 references (44%) did not claim to be randomized or were not randomized at a level allowing comparison of pregnancy outcomes (e.g. randomization of embryos to intervention, then best embryos transferred regardless of randomization); 32 (32%) did not mention any pregnancy outcomes; and 18 references (18%) were not considered to report fertility trials, i.e. not all patients in the trial or in a pre-identified subgroup had live birth as main aim, although this may have been reported for some of the patients (e.g. study of the impact of a procedure on future fertility when not all patients will attempt to become pregnant or study of interventions to improve sperm count in healthy volunteers).
One hundred and sixty-four references were available for review. The quality of these references was assessed according to the Cochrane Handbook (Higgins and Green, 2005) and the CONSORT requirements, focusing on the following aspects:
- Randomization method.
- Allocation concealment: we have assumed that when no information is present, allocation was not concealed. A distinction has also been made between trials where allocation was clearly adequately concealed and those where there is some mention of concealment, but it is unclear whether this was achieved adequately.
- Trial design: crossover trials are unsuitable for ‘terminal event’ outcomes such as pregnancy and birth that preclude entry to subsequent phases.
- Patient flow: the number of patients randomized, excluded and analysed should always be made clear in reports. Knowing the number of women initially randomized to treatment groups, as well as the number of women with positive outcomes, is essential to carry out an ITT approach.
- Unit-of-analysis errors: these errors occur when the unit of randomization is not the unit used as a denominator in the analysis and presentation of results. Although it may be acceptable to present some results in this form, it should not replace the presentation of the ‘per randomized woman’ results and should not be used in the main analysis. For example, when women are randomized to receiving multiple cycles of a given treatment, and the number of pregnancies per cycle are considered in the analysis, a unit-of-analysis error has occurred. We assessed whether such errors were present for any pregnancy outcome or adverse event and whether the correct results could be extracted from the information provided in the report.
- Adverse events: the number of miscarriages and ectopic and multiple pregnancies are important adverse events in subfertility and should be reported even if none occurred. Failure to disclose any adverse events may be considered evidence of selective reporting (Hahn et al., 2000, 2002).
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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The Cochrane MDSG database contained references to trials that have been published in 152 different journals. It was decided that the two main fertility journals [Fertility & Sterility (F&S) and Human Reproduction (HR)] should be analysed separately, as they publish the bulk of the trials in this field, are perceived as high-quality journals and have been the subject of a previous quality review (Vail and Gardener, 2003
). In the 3 years considered, F&S published 61 trials, HR 50 trials and the ‘other’ journals 53 trials. The specialty of the main intervention was recorded as ‘Laboratory’ for trials where the intervention does not take place directly on the patient (e.g. different culture media for oocyte fertilization), ‘Medical’ for drug trials and ‘Surgical’ for trials where the intervention involves anaesthetics or a surgical procedure (e.g. different types of catheter for embryo transfer) (Table I). ‘Main intervention’ was defined as the intervention of chief interest in the study or the ‘new’ intervention, i.e. the reason the trial was conducted.
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Randomization method
In this review, 81 trials (49%) were found not to have provided details on the randomization method. A further 24 (15%) had in fact allocated treatments in a non-random way, despite the ‘randomized’ claim. Of these, 10 used alternate treatment assignment and 11 used odd/even patient number, date of treatment, date of birth etc. to allocate patients to treatments. Three trials used totally ad hoc methods of treatment assignment (two studies allowed patients to choose their own preferred treatment and one chose controls as being the patients to whom treatment could not be applied due to weekends). More surgical trials used non-random methods of allocation as opposed to medical or laboratory trials. The proportion of trials using clearly non-random methods of allocation was similar for the 3 years considered (Figure 1). The proportion on trials describing an adequate randomization method increased from 16% in 1990 to 40% in 1996 and then 48% in 2002. HR published fewer non-randomized reports and had a higher proportion of trials accurately describing the allocation method than the other journals (Table II).
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Allocation concealment
Allocation concealment is always possible and is an important indicator of the methodological quality of a randomized control trial. In the CONSORT checklist, not only are authors required to detail how the allocation sequence was generated, but also whether this sequence was concealed until the treatment was assigned. The most secure method of allocation concealment is third-party allocation, where someone not involved in the trial holds the allocation schedule. However, properly sealed, serially numbered, opaque envelopes containing the allocation schedule are also acceptable. Statements of the form ‘the doctor was blinded to treatment allocation’ were classified as ‘unclear concealment’.
Of all the trials assessed, only 17 (10%) had described adequate forms of allocation concealment and 11 of these were published in 2002 (Figure 1). Although the leading fertility journals publish most of the trials with adequate allocation concealment (of the 17 trials, F&S 8 and HR 7), the total number of clearly adequately concealed trials is disappointing: 17 of 164 (10%) (Table II). Even assuming that in reports classified as ‘unclear’ allocation was adequately concealed (albeit poorly reported), the number of concealed trials only rises to 39 of 164 (24%).
Trial design (crossover trials)
The number of published trials using crossover designs decreased considerably from 11 trials (24%) in 1990 to 8 (13%) in 1996 and then to just 2 trials (3%) in 2002 (Table II). There was a preference of authors of certain types of surgical trial (e.g. different methods of insemination/embryo transfer) to use crossover designs. Of the 21 crossover trials reviewed, 19 may have been adequately randomized (of which only five provide details of the randomization, two of which also had adequately concealed the allocation schedule). Only two crossover trials were classified as possibly randomized and reported pre-crossover pregnancy data.
Patient flow
As a minimum, trials that are identified as suitable for inclusion in Cochrane Reviews should have adequate randomization of patients to interventions. Often this is interpreted as merely stating that patients were randomly assigned to the treatments, without further detail, and there being no evidence of this being done in either a systematic or a haphazard way. Of the 164 subfertility trials reviewed, we found that only 140 (85%) satisfied these criteria. Of these, only 99 (60%) provided details on the number of women initially randomized to each group, as opposed to just the number of women analysed in each group, eight of which did not adequately report the number of women in each group achieving a pregnancy: three were crossover trials with first-stage data not extractable, three reported pregnancies only as percentages and the actual numbers were not extractable, one had contradictory numbers in the tables and text and the other stated only that there had been no increase in the pregnancy rate. Only 91 trials (55%) reported sufficient details on the number of women randomized and clinical pregnancies for each group; 57 also reported sufficient details on the number of ongoing pregnancies, of which 17 also reported sufficient details on the number of live births in each group. If strict quality criteria are applied, only 10 of the 164 (6%) trials assessed adequately reported on the randomization and allocation concealment methods, of which only three (all published in 2002, in HR and F&S) had sufficient details extractable to allow for an ITT analysis of the outcome ‘live birth’ (Figure 2).
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Unit-of-analysis errors
Of the 140 trials that may have used adequate randomization, 41 (29%) failed to report information on the number of women actually randomized to each treatment group (Figure 2), including 17 that reported the number of women analysed but where the number of post-randomization dropouts was unclear. For the remaining 24 trials (11 of which were crossover), the unit-of-analysis errors, such as reporting only the number of cycles in each group instead of number of women, were the main reason why the number of women in each treatment arm was not extractable. The number of trials with the unit-of-analysis errors and without the essential data extractable was lower in 2002 (5 trials) than in the previous years examined (11 in 1990 and 8 in 1996). F&S published 5 such trials in the 3 years considered, compared to 11 published by HR and 8 by the other journals.
Pregnancy-related adverse events
Of the 99 trials that may have used adequate randomization and reported sufficient details on the number of women randomized to each group, 58 had details extractable on the number of miscarriages for each group, 27 had details on the number of ectopic pregnancies and 36 had details on the number of multiple pregnancies in each group. A few reports mentioned the number of miscarriages and ectopic and multiple pregnancies in some way (e.g. as total number of events in the trial or for certain subgroups), but results for each randomized group were not extractable (Table III). Twenty trials (20%) had details extractable for all three adverse events, and three reports did not mention any of them. Miscarriages were fairly widely reported in the leading subfertility journals (F&S and HR), but reporting of ectopic and multiple pregnancies was less common.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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The effect of the CONSORT statement on the quality of RCTs has been assessed in the past: Moher et al. (2001a
) concluded that the publication of CONSORT had had an impact on certain aspects of the quality of reporting of RCTs by 1998, when compared with 1994. Devereaux et al. (2002) found that the promotion of the CONSORT checklist to authors was associated with better reporting. Other studies have suggested that the awareness of the problems of poor reporting of medical research (Altman, 1994; Schulz et al., 1994, 1995) was already pushing up the quality of RCT reports before the publication of the CONSORT statement. Nevertheless, all studies concluded that there was still great scope for improvement in trial quality, particularly regarding the method of generating and concealing the treatment allocation sequence, which agrees with the results of the present review.
The proportion of subfertility trials found to have adequately reported random treatment allocation in 1990 and 1996 was 30%. These results are similar to those obtained in previous pre-CONSORT reviews of subfertility and obstetrics and gynaecology, where 29 and 32% of references were found to have adequately reported the randomization method (Vandekerckhove et al., 1993; Schulz et al., 1994), but lower than the 49% (Altman and Doré, 1990) and 52% (Kjaergard et al., 1999) from reviews of trials published only in high-impact journals. In 2002, 56% of trials published in F&S and HR adequately reported a random method of treatment allocation compared with 64% of trials published in 2001 (Vail and Gardener, 2003). Reviews of the quality of trials published after CONSORT have found proportions of 23–60% in general medical fields (Devereaux et al., 2002; Hill et al., 2002), setting subfertility trials in the upper half of this range.
We have seen that 17% of pre-CONSORT and 37% of post-CONSORT trials mention some form of allocation concealment (even if not completely clear). Considering only the main subfertility journals (F&S and HR), we obtain 20 and 40% as pre- and post-CONSORT proportions, respectively. This is comparable to other results in the literature: 23–32%, pre-CONSORT (Schulz et al., 1994, 1995, 1996) and 33% after CONSORT (Vail and Gardener, 2003).
In the years included in this review, the proportions of trials reporting both adequate randomization and allocation concealment were 10% (6/59) after CONSORT and 4% (4/105) before CONSORT. If we include reports with unclear descriptions of allocation concealment, these proportions rise to 9 and 19% before and after CONSORT, respectively, rising again to 10 and 24%, respectively, when only the two main subfertility journals are considered. The overall proportion of the reviewed trials reporting adequate randomization and allocation concealment was 6% (10/164).
Of the aspects specific to subfertility, it is noteworthy that the number (and proportion) of crossover trials published in each year decreased. However, reporting of pregnancy-related adverse events, the timing of randomization and the number of women randomized to each treatment is still poor.
The unit-of-analysis errors were again identified as a major cause of poor quality in the subfertility literature. This has been noted as a common problem in other areas, such as ophthalmology (Newcombe and Duff, 1987) or dentistry (Blomquist, 1985), where each patient contributes multiple observations (two eyes and multiple teeth) and is covered in the BMJ’s Statistics Notes (Altman and Bland, 1997). Survival analysis, hierarchical models and other statistical methods have been developed to adequately analyse studies where each patient contributes multiple observations. In the area of subfertility, there is the added complication of informative censoring: reasons for not participating in subsequent cycles may depend on prognosis following a first unsuccessful cycle. It is therefore not clear whether the direct application of methods developed for other areas would yield valid analyses in subfertility, and this is currently the subject of ongoing statistical research.
In this review, only 10 trials provided evidence of having adequately allocated patients to interventions, of which only three had extractable details on the number of women randomized, ongoing pregnancies and the number of births in each group. Given that poor reporting is often associated with poor methodological quality (Schulz et al., 1995), much still needs to be done to improve the quality of RCTs in subfertility. Although some of the issues detected in this review relate to fundamental design flaws, others are exclusively due to poor reporting. This suggests that although many journals claim to have adopted the CONSORT statement, referees and editors need to be more aware of its requirements.
Our concern is the ability to include data from published trials in Cochrane Reviews of relevant interventions for subfertility. The quality criteria of Cochrane Reviews of RCTs were taken as the basis for our own definition of quality. We have found that a general improvement in reporting quality would mean that meta-analyses would be substantially more informative since fewer trials would be excluded because of the lack of information being provided. In the meantime, systematic reviewers will need to continue contacting authors for more detailed information.
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Conflicts of interest |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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Sofia Dias and Andy Vail are statistical editors for the Cochrane Menstrual Disorders and Subfertility Group.
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Appendix 1. Included studies |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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Aboulghar M, Mansour R, Serour G, Sattar M, Awad M, Amin Y. (1990) Transvaginal ultrasonic needle guided aspiration of pelvic inflammatory cystic masses before ovulation induction for in vitro fertilization. Fertil Steril 53:311–314.[Web of Science][Medline]
Aboulghar MA, Mansour RT, Serour GI, Sattar MA, Amin YM. (1996a) Intracytoplasmic sperm injection and conventional in vitro fertilization for sibling oocytes in cases of unexplained infertility and borderline semen. J Assist Reprod Genet 13:38–42.[CrossRef][Web of Science][Medline]
Aboulghar MA, Mansour RT, Serour GI, Amin YM, Kamal A. (1996b) Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters. Fertil Steril 66:753–756.[Web of Science][Medline]
Almagor M, Bejar C, Kafka I, Yaffe H. (1996) Pregnancy rates after communal growth of preimplantation human embryos in vitro. Fertil Steril 66:394–397.[Web of Science][Medline]
Andersen AN, Popovic-Todorovic B, Schmidt KT, Loft A, Lindhard A, Hojgaard A, Ziebe S, Hald F, Hauge B, Toft B. (2002) Progesterone supplementation during early gestations after IVF or ICSI has no effect on the delivery rates: a randomized controlled trial. Hum Reprod 17:357–361.
Antoine J, Salat-Baroux J, Alvarez S, Cornet D, Tibi C, Mandelbaum J, Plachot M. (1990) Ovarian stimulation using human menopausal gonadotropins with/without LHRH analogues in a long protocol for in-vitro fertilization: a prospective randomized comparison. Hum Reprod 5:565–569.
Arcaini L, Bianchi S, Baglioni A, Marchini M, Tozzi L, Fedele L. (1996) Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study. J Reprod Med 41:614–618.[Web of Science][Medline]
Awounga A, Waterstone J, Oyesanya O, Curson R, Nargund G, Parsons J. (1996) A prospective randomized study comparing needles of different diameters for transvaginal ultrasound-directed follicle aspiration. Fertil Steril 65:109–113.[Web of Science][Medline]
Balasch J, Fabregues F, Creus M, Moreno V, Puerto B, Penarrubia J, Carmona F, Vanrell JA. (1996) Pure and highly purified follicle-stimulating hormone alone or in combination with human menopausal gonadotrophin for ovarian stimulation after pituitary suppression in in-vitro fertilization. Hum Reprod 11:2400–2404.
Barash A, Shoham Z, Lunenfeld B, Segal I, Insler V, Borenstein R. (1990) Can premature luteinization in superovulation protocols be prevented by aspiration of an ill-timed leading follicle? Fertil Steril 53:865–869.[Web of Science][Medline]
Battaglia C, Regnani G, Marsella T, Facchinetti F, Volpe A, Venturoli S, Flamigni C. (2002) Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study. Hum Reprod 17:659–665.
Belaisch-Allart J, Allart J, Dufetre C, Briot P, Stalla Bourdillon A. (1990a) An improved use of buserelin in ovarian stimulation for in-vitro fertilization. Hum Reprod 5:573–574.
Belaisch-Allart J, De Mouzon J, Lapousterle C, Mayer M. (1990b) The effect of HCG supplementation after combined GnRH agonist/hMG treatment in an IVF programme. Hum Reprod 5:163–166.
Bider D, Menashe Y, Goldenberg M, Dulitzky M, Lifshitz A, Dor J. (1996a) Dexamethasone as an adjuvant therapy for anovulatory, normoandrogenic patients during ovulation induction with exogenous gonadotropins. J Assist Reprod Genet 13:613–616.[CrossRef][Web of Science][Medline]
Bider D, Amoday I, Yonesh M, Yemini Z, Mashiach S, Dor J. (1996b) Glucocorticoid administration during transfer of frozen-thawed embryos: a prospective, randomized study. Fertil Steril 66:154–156.[Web of Science][Medline]
Bider D, Amoday I, Tur-Kaspa I, Livshits A, Dor J. (1996c) The addition of a glucocorticoid to the protocol of programmed oocyte retrieval for in-vitro fertilization – a randomised study. Hum Reprod 11:1606–1608.
Blumenfeld Z and Amit T. (1996) The role of growth hormone (GH), GH-receptor and GH-binding protein in reproduction and ovulation induction. J Pediatr Endocrinol Metab 9:145–162.[Web of Science][Medline]
Bovenschen JL, Lawrence KA, Abuzeid M, Jones ML, Achwal M, Verrill H, Gerbasi F. (2002) Remifentanil and fentanyl concentrations in follicular fluid during transvaginal oocyte retrieval. Middle East Fertil Soc J 7:18–23.
Busacca M, Fusi FM, Brigante C, Bonzi V, Gonfiantini C, Vignali M, Ferrari A. (1996) Use of growth hormone-releasing factor in ovulation induction in poor responders. J Reprod Med 41:669–703.
Buvat J, Marcolin G, Guittard C, Herbaut J, Louvet A, Dehaene J. (1990) Luteal support after luteinizing hormone-releasing hormone agonist for in vitro fertilization: superiority of human chorionic gonadotropin over oral progesterone. Fertil Steril 53:490–494.[Web of Science][Medline]
Byrd W, Bradshaw K, Carr B, Edman C, Odom J, Ackerman G. (1990) A prospective randomized study of pregnancy rates following intrauterine and intracervical insemination using frozen donor sperm. Fertil Steril 53:521–527.[Web of Science][Medline]
Cedrin-Durnerin I, Bulwa S, Herve F, Martin Pont B, Uzan M, Hugues JN. (1996) The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment. Hum Reprod 11:1859–1863.
Check JH. (1996) Low-dose gonadotrophin stimulation for luteal phase defects – does absence of LH help pregnancy rates? Del Med J 68:223–226.[Medline]
Clifford K, Rai R, Watson H, Franks S, Regan L. (1996) Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial. BMJ 312:1508–1511.
Comhaire F. (1990) Treatment of idiopathic testicular failure with high-dose testosterone undecenoate: a double-blind pilot study. Fertil Steril 54:689–693.[Web of Science][Medline]
Coroleu B, Barri PN, Carreras O, Martinez F, Parriego M, Hereter L, Parera N, Veiga A, Balasch J. (2002a) The influence of the depth of embryo replacement into the uterine cavity on implantation rates after IVF: a controlled, ultrasound-guided study. Hum Reprod 17:341–346.
Coroleu B, Barri PN, Carreras O, Martinez F, Veiga A, Balasch J. (2002b) The usefulness of ultrasound guidance in frozen-thawed embryo transfer: a prospective randomized clinical trial. Hum Reprod 17:2885–2890.
Coulson C, McLhlin EA, Harris S, Ford WCL, Hull MGR. (1996) Randomized controlled trial of cervical cap with intracervical reservoir versus standard intracervical injection to inseminate cryopreserved donor semen. Hum Reprod 11:84–87.
Czeizel AE, Metneki J, Dudas I. (1996) The effect of preconceptional multivitamin supplementation on fertility. Int J Vitam Nutr Res 66:55–58.[Web of Science][Medline]
Dale B, Fiorentino A, De Simone ML, Di Matteo L, Di Frega AS, Wilding M, Fehr P, Bassan E, Lo Giudice C, Maselli A, et al. (2002) Zygote versus embryo transfer: a prospective randomized multicenter trial. J Assist Reprod Genet 19:456–461.[CrossRef][Web of Science][Medline]
Daures J, Hedon B, Arnal F, Badoc E, Boulot P, Huet J, Simondon E, Momas I, Deschamps F, Cristol P, et al. (1990) Early or late monitoring of stimulation of ovulation for in-vitro fertilization? A methodological discussion of a randomized study. Hum Reprod 5:138–142.
Deaton J, Gibson M, Blackmer K, Nakajima S, Badger G, Brumsted J. (1990) A randomized controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility on surgically corrected endometriosis. Fertil Steril 54:1083–1088.[Web of Science][Medline]
De Geyter C, De Geyter M, Bals-Pratsch M, Nieschlag E, Schneider PG. (1996) Experience with transvaginal ultrasound – guided aspiration of supernumeracy follicles for the prevention of multiple pregnancies after ovulation induction and intrauterine insemination. Fertil Steril 65:1163–1168.[Web of Science][Medline]
De Hellebaut SSP, Dozortsev D, Onghena A, Qian C, Dhont M. (1996) Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study. J Assist Reprod Genet 13:19–22.[CrossRef][Web of Science][Medline]
Devreker F, Govaerts I, Bertrand E, Van den Bergh M, Gervy C, Englert Y. (1996) The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate. Fertil Steril 65:122–126.[Web of Science][Medline]
Dickey RP, Thornton M, Nichols J, Marshall DC, Fein SH, Nardi RV. Bravelle IVF Study Group. (2002) Comparison of the efficacy and safety of a highly purified human follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro fertilization: a prospective, randomized study. Fertil Steril 77:1202–1208.[CrossRef][Web of Science][Medline]
Ditkoff EC and Sauer MV. (1996) A combination of norethindrone acetate and leuprolide acetate blocks the gonadotrophin releasing hormone agonistic response and minimizes cyst formation during ovarian stimulation. Hum Reprod 11:1035–1037.
Drakakis P, Loutradis D, Kallianidis K, Bletsa R, Milingos S, Dionyssiou-Asteriou A, Michalas S. (2002a) A comparative study of the effect of ovarian stimulation protocols with different gonadotropin preparations on the biological and clinical parameters of the outcome of intracytoplasmic sperm injection. Clin Exp Obstet Gynecol 29:286–289.[Medline]
Drakakis P, Loutradis D, Kallianidis K, Milingos S, Dionyssiou-Asteriou A, Michalas S. (2002b) The clinical efficacy of recombinant FSH (r-FSH) as compared to highly purified urinary gonadotrophin (hMG-FD) and the use of a low starting dose of r-FSH in IVF or ICSI. A randomized prospective study. Ital J Gynaecol Obstet 14:64–68.
Dumoulin J, Evers J, Offermans J, Bras M, Pieters M, Geraedts J. (1990) Human in vitro fertilization using spermatozoa capacitated in hyperosmotic media. Gynecol Obstet Invest 30:165–168.[CrossRef][Web of Science][Medline]
Ebner T, Moser M, Yaman C, Sommergruber M, Hartl J, Jesacher K, Tews G. (2002) Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI. Hum Reprod 17:1317–1320.
Edelstein M, Bryzyski R, Jones G, Simonetti S, Muasher S. (1990) Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression. Fertil Steril 53:103–106.[Web of Science][Medline]
Ehimen Egbase P, Al Sharhan M, Grudzinskas JG. (2002) A comparison of a step-up protocol with high fixed dose gonadotropin administration for controlled ovarian stimulation in obese patients without polycystic ovarian syndrome: a prospective randomized trial. Middle East Fertil Soc J 7:199–204.
El Mowafi DM and El Hendy UA. (2002) Follicular fluid MMP-2 and MMP-9 in stimulated IVF patients. Middle East Fertil Soc J 7:24–30.
The European and Israeli Study Group on Highly Purified Menotropin Versus Recombinant Follicle Stimulating Hormone. (2002) Efficacy and safety of highly purified menotropin versus recombinant follicle-stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection cycles: a randomized, comparative trial. Fertil Steril 78:520–528.[CrossRef][Web of Science][Medline]
Everhardt E, Dony J, Jansen H, Lemmens W, Doesburg W. (1990) Improvement of cervical mucus viscoelasticity and sperm penetration with sodium bicarbonate douching. Hum Reprod 5:133–137.
Farquhar CM, Williamson K, Gudex G, Johnson NP, Garland J, Sadler L. (2002) A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate–resistant polycystic ovary syndrome. Fertil Steril 78:404–411.[CrossRef][Web of Science][Medline]
Federman C, Dumesic D, Boone W, Shapiro S. (1990) Relative efficiency of therapeutic donor insemination using a luteinizing hormone monitor. Fertil Steril 54:489–492.[Web of Science][Medline]
Feldberg D, Goldman G, Dicker D, Ashkenazi J, Yeshaya A, Goldman J. (1990) The value of GnRH agonists in the treatment of failed cycles in an IVF-ET program: a comparative study. Eur J Obstet Gynecol Reprod Biol 34:103–109.[CrossRef][Web of Science][Medline]
Ferrier A, Rasweiler J, Bedford J, Prey K, Berkeley A. (1990) Evaluation of leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins for in vitro fertilization or gamete intrafallopian transfer. Fertil Steril 54:90–95.[Web of Science][Medline]
Fox JH, Jackson KV, Rein MS, Hornstein MD, Clarke RN, Friedman AJ. (1996) A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program. Fertil Steril 65:598–602.[Web of Science][Medline]
Garcia-Velasco JA, Isaza V, Martinez Salazar J, Landazabal A, Requena A, Remohi J, Simon C. (2002) Transabdominal ultrasound-guided embryo transfer does not increase pregnancy rates in oocyte recipients. Fertil Steril 78:534–539.[CrossRef][Web of Science][Medline]
Gerhard I, Roth B, Eggert-Kruse W, Runnebaum B. (1990) Effects of kallikrein on sperm motility-capillary tube test and pregnancy rate in an AIH program. Arch Androl 24:129–145.[Web of Science][Medline]
Germond M, Capelli P, Bruno G, Vesnaver S, Senn A, Rouge N, Biollaz J. (2002) Comparison of the efficacy and safety of two formulations of micronized progesterone (Ellios and Utrogestan) used as luteal phase support after in vitro fertilization. Fertil Steril 77:313–317.[CrossRef][Web of Science][Medline]
Gianaroli L, Fiorentino A, Magli MC, Ferraretti AP, Montanaro N. (1996a) Prolonged sperm-oocyte exposure and high sperm concentration affect human embryo viability and pregnancy rate. Hum Reprod 11:2507–2511.
Gianaroli L, Magli MC, Ferraretti AP, Fiorentino A, Tosti E, Panzella S, Dale B. (1996b) Reducing the time of sperm oocyte interaction in human in-vitro fertilization improves the implantation rate. Hum Reprod 11:166–171.
Glazener C, Coulson C, Lambert P, Watt E, Hinton R, Kelly N, Hull M. (1990) Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates. Gynecol Endocrinol 4:75–83.[Web of Science][Medline]
Gonen Y and Casper RF. (1990) Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth. Hum Reprod 5:670–674.
Gonen Y, Balakier H, Powell W, Casper R. (1990) Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization. J Clin Endocrinol Metab 71:918–922.
Gregoriou O, Vitoratos N, Papadias C, Konidaris S, Gargaropoulos A, Rizos D. (1996) Pregnancy rates in gonadotrophin stimulated cycles with timed intercourse or intrauterine insemination for the treatment of male subfertility. Eur J Obstet Gynecol Reprod Biol 64:213–216.[CrossRef][Web of Science][Medline]
Griesinger G, Franke K, Kinast C, Kutzelnigg A, Riedinger S, Kulin S, Kaali SG, Feichtinger W. (2002) Ascorbic acid supplement during luteal phase in IVF. J Assist Reprod Genet 19:164–168.[CrossRef][Web of Science][Medline]
Grigoriou O, Konidaris S, Antonaki V, Papadias C, Antoniou G, Gargaropoulos A. (1996) Corticosteroid treatment does not improve the results of intrauterine insemination in male subfertility caused by antisperm antibodies. Eur J Obstet Gynecol Reprod Biol 65:227–230.[CrossRef][Web of Science][Medline]
Hendry W, Hughes L, Scammell G, Pryor J, Hargreave T. (1990) Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa. Lancet 335:85–88.[CrossRef][Web of Science][Medline]
Herman A, Ron El R, Golan A, Raziel A, Soffer Y, Caspi E. (1990) Pregnancy rate and ovarian hyperstimulation after luteal human chorionic gonadotropins in in vitro fertilization stimulated with gonadotropin-releasing hormone analog and menotropins. Fertil Steril 53:92–96.[Web of Science][Medline]
Herman A, Raziel A, Strassburger D, Soffer Y, Bukovsky I, Ron El R. (1996) The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone. Hum Reprod 11:1552–1557.
Homburg R, Eshel A, Kilborn J, Adams J, Jacobs H. (1990a) Combined luteinizing hormone releasing hormone analogue and exogenous gonadotropins for the treatment of infertility associated with polycystic ovaries. Hum Reprod 5:32–35.
Homburg R, West C, Torresani T, Jacobs H. (1990b) Cotreatment with human growth hormone and gonadotropins for induction of ovulation: a controlled clinical trial. Fertil Steril 53:254–260.[Web of Science][Medline]
Hoomans EHM and Mulder BB. (2002) A group-comparative, randomized, double-blind comparison of the efficacy and efficiency of two fixed daily dose regimens (100- and 200-IU) of recombinant follicle stimulating hormone (rFSH, Puregon) in Asian women undergoing ovarian stimulation for IVF/ICSI. J Assist Reprod Genet 19:470–476.[CrossRef][Web of Science][Medline]
Hovatta O, Kurunmaki H, Tiitinen A, Lahteenmaki P, Koskimies A. (1990) Direct intraperitoneal or intrauterine insemination and superovulation in infertility treatment: a randomized study. Fertil Steril 54:339–341.[Web of Science][Medline]
Hsieh YY, Huang CC, Cheng TC, Chang CC, Tsai HD, Lee MS. (2002) Laser-assisted hatching of embryos is better than the chemical method for enhancing the pregnancy rate in women with advanced age. Fertil Steril 78:179–182.[CrossRef][Web of Science][Medline]
Hugues JN, Cedrin-Durnerin I, Avril C, Bulwa S, Herve F, Uzan M. (1996) Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome. Hum Reprod 11:2581–2584.
Hurd WW, Randolph JF, Christman GM, Ansbacher R, Menge AC, Gell JS. (1996) Luteal support with both estradiol and progesterone after clomiphene citrate stimulation for in vitro fertilization. Fertil Steril 66:587–592.[Web of Science][Medline]
Isik AZ, Gokmen O, Zeyneloglu HB, Kara S, Keles G, Gulekli B. (1996) Intravenous albumin prevents moderate-severe ovarian hyperstimulation in in-vitro fertilization patients: a prospective, randomized and controlled study. Eur J Obstet Gynecol Reprod Biol 70:179–183.[CrossRef][Web of Science][Medline]
Jinno M, Ubukata Y, Satou M, Katsumata Y, Yoshimura Y, Nakamura Y. (1996) An improvement in the embryo quality and pregnancy rate by the pulsatile administration of human menopausal gonadotropin in patients with previous unsuccessful in vitro fertilization attempts. Fertil Steril 65:382–386.[Web of Science][Medline]
Johnson P and Pearce J. (1990) Recurrent spontaneous abortion and polycystic ovarian disease: comparison of two regimens to induce ovulation. BMJ 300:154–156.
Kahraman S, Tasdemir M, Tasdemir I, Vicdan K, Ozgur S, Polat G, Islk AZ, Biberoglu K, Vanderzwalmen P, Nijs M, et al. (1996) Pregnancies achieved with testicular and ejaculated spermatozoa in combination with intracytoplasmic sperm injection in men with totally or initially immotile spermatozoa in the ejaculate. Hum Reprod 11:1343–1346.
Karaki RZ, Samarraie SS, Younis NA, Lahloub TM, Ibrahim MH. (2002) Blastocyst culture and transfer: a step toward improved in vitro fertilization outcome. Fertil Steril 77:114–118.[CrossRef][Web of Science][Medline]
Karande V, Hazlett D, Vietzke M, Gleicher N. (2002) A prospective randomized comparison of the Wallace catheter and the Cook Echo-Tip (R) catheter for ultrasound-guided embryo transfer. Fertil Steril 77:826–830.[CrossRef][Web of Science][Medline]
Kim CH, Cho YK, Mok JE. (1996a) Simplified ultralong protocol of gonadotrophin releasing hormone agonist for ovulation induction with intrauterine insemination in patients with endometriosis. Hum Reprod 11:398–402.
Kim CH, Cho YK, Mok JE. (1996b) The efficacy of immunotherapy in patients who underwent superovulation with intrauterine insemination. Fertil Steril 65:133–138.[Web of Science][Medline]
Kinget K, Nijs M, Cox AM, Janssen M, Jacobs P, Bosmans E, Ombelet W. (2002) A novel approach for patients at risk for ovarian hyperstimulation syndrome: elective transfer of a single zona-free blastocyst on day 5. Reprod Biomed Online 4:51–55.[Medline]
Kocak M, Caliskan E, Simsir C, Haberal A. (2002) Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril 77:101–106.[Web of Science][Medline]
Kondaveeti-Gordon U, Harrison RF, Barry-Kinsella C, Gordon AC, Drudy L, Cottell E. (1996) A randomized prospective study of early follicular or midluteal initiation of long protocol gonadotropin-releasing hormone in an in vitro fertilization program. Fertil Steril 66:582–586.[Web of Science][Medline]
Kubik C, Guzick D, Berga S, Zelenik A. (1990) Randomized-prospective trial of leuprolide acetate and conventional superovulation in first cycles of in vitro fertilization and gamete intrafallopian transfer. Fertil Steril 54:836–841.[Web of Science][Medline]
Kupferminc M, Lessing J, Amit A, Yovel I, David M, Peyser M. (1990) A prospective randomized trial of human chorionic gonadotropin or dydrogesterone support following in-vitro fertilization and embryo transfer. Hum Reprod 5:271–273.
Larsen T, Larsen JF, Schioler V, Bostofte E, Felding C. (1990) Comparison of urinary human follicle-stimulating hormone and human menopausal gonadotropin for ovarian stimulation in polycystic ovarian syndrome. Fertil Steril 53:426–431.[Web of Science][Medline]
Levran D, Dor J, Rudak E, Nebel L, Ben-Shlomo I, Ben-Rafael Z, Mashiach S. (1990) Pregnancy potential of human oocytes – the effect of cryopreservation. N Engl J Med 323:1153–1156.[Abstract]
Levron J, Shulman A, Bider D, Seidman D, Levin T, Dor J. (2002) A prospective randomized study comparing day 3 with blastocyst-stage embryo transfer. Fertil Steril 77:1300–1301.[CrossRef][Web of Science][Medline]
Lewis-Jones DI, Kynaston HG, Lynch RV, Desmond AD, Entwistle PA. (1996) Antibiotic treatment of leucospermia in subfertile males. Arch STD/HIV Res 10:65–72.
Leyendecker G, Bernart W, Bremen T, Beck H, Kunz G, Waibel S, Blum A, Stenger P, Kaplan-Reiterer H. (1990) Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/hMG-stimulated IVF cycles. Hum Reprod 5:52–55.
Lisi F, Rinaldi L, Fishel S, Lisi R, Pepe GP, Picconeri MG, Campbell A. (2002) Use of recombinant LH in a group of unselected IVF patients. Reprod Biomed Online 5:104–108.[Medline]
Livingstone M. (2002) Single blastocyst transfer: a prospective randomised trial. R Aust NZ Coll Obstet Gynaecol 1–53.
Lok IH, Chan MTV, Chan DLW, Cheung LP, Haines CJ, Yuen PM. (2002) A prospective randomized trial comparing patient-controlled sedation using propofol and alfentanil and physician-administered sedation using diazepam and pethidine during transvaginal ultrasound-guided oocyte retrieval. Hum Reprod 17:2101–2106.
Ludwig M, Schwartz P, Babahan B, Katalinic A, Weiss JM, Felberbaum R, Al Hasani S, Diedrich K. (2002a) Luteal phase support using either Crinone 8% or Utrogest: results of a prospective, randomized study. Eur J Obstet Gynecol Reprod Biol 103:48–52.[CrossRef][Web of Science][Medline]
Ludwig M, Katalinic A, Banz C, Schroder AK, Loning M, Weiss JM, Diedrich K. (2002b) Tailoring the GnRH antagonist cetrorelix acetate to individual patient’s needs in ovarian stimulation for IVF: results of a prospective, randomized study. Hum Reprod 17:2842–2845.
Macklon NS, Pieters MHEC, Hassan MA, Jeucken PHM, Eijkemans MJC, Fauser BCJM. (2002) A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development. Hum Reprod 17:2700–2705.
Mahadevan MM, Miller MM, Moutos DM. (1996) Improved human zygote development in a modified Ham’s F10 medium in vitro. J Assist Reprod Genet 13:722–725.[CrossRef][Web of Science][Medline]
Maier U and Hienert G. (1990) Tamoxifen and kallikrein in therapy of oligoasthenozoospermia: results of a randomized study. Eur Urol 17:223–225.[Web of Science][Medline]
Malkawi HY and Qublan HS. (2002) The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome. Saudi Med J 23:663–666.[Web of Science][Medline]
Mamas L. (1996) Higher pregnancy rates with a simple method for fallopian tube sperm perfusion, using the cervical clamp double nut bivalve speculum in the treatment of unexplained infertility: a prospective randomized study. Hum Reprod 11:2618–2622.
Manau D, Fabregues F, Arroyo V, Jimenez W, Vanrell JA, Balasch J. (2002) Hemodynamic changes induced by urinary human chorionic gonadotropin and recombinant luteinizing hormone used for inducing final follicular maturation and luteinization. Fertil Steril 78:1261–1267.[CrossRef][Web of Science][Medline]
Mansour R, Aboulghar M, Serour G. (1990) Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization. Fertil Steril 54:678–681.[Web of Science][Medline]
Martinez AR, Bernardus RE, Voorhorst FJ, Vermeiden JP, Schoemaker J. (1990) Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study. Fertil Steril 53:847–853.[Web of Science][Medline]
Matorras R, Gorostiaga A, Diez J, Corcostegui B, Pijoan JI, Ramon O, Rodriguez-Escudero FJ. (1996) Intrauterine insemination with frozen sperm increases pregnancy rates in donor insemination cycles under gonadotropin stimulation. Fertil Steril 65:620–625.[Web of Science][Medline]
Matorras R, Diaz T, Corcostegui B, Ramon O, Pijoan JI, Rodriguez-Escudero FJ. (2002a) Ovarian stimulation in intrauterine insemination with donor sperm: a randomized study comparing clomiphene citrate in fixed protocol versus highly purified urinary FSH. Hum Reprod 17:2107–2111.
Matorras R, Urquijo E, Mendoza R, Corcostegui B, Exposito A, Rodriguez Escudero FJ. (2002b) Ultrasound-guided embryo transfer improves pregnancy rates and increases the frequency of easy transfers. Hum Reprod 17:1762–1766.
McDonald JA and Norman RJ. (2002) A randomized controlled trial of a soft double lumen embryo transfer catheter versus a firm single lumen catheter: significant improvements in pregnancy rates. Hum Reprod 17:1502–1506.
van der Meer M, Hompes PG, Scheele F, Schoute E, Popp-Snijders C, Schoemaker J. (1996) The importance of endogenous feedback for monofollicular growth in low-dose step-up ovulation induction with follicle-stimulating hormone in polycystic ovary syndrome: a randomized study. Fertil Steril 66:571–576.[Web of Science][Medline]
Micic S, Tulic C, Dotlic R. (1990) Kallikrein therapy of infertile men with varicocele and impaired sperm motility. Andrologia 22:179–183.[Web of Science][Medline]
Mitchell R, Buckler HM, Matson P, Lieberman B, Burger HG, Hilton B, Horne G, Dyson M, Robertson WR. (1996) Oestradiol and immunoreactive inhibin-like secretory patterns following controlled ovarian hyperstimulation with urinary (Metrodin) or recombinant follicle stimulating hormone (Puregon). Hum Reprod 11:962–967.
Mochtar MH, Hogerzeil HV, Mol BW. (1996) Progesterone alone versus progesterone combined with HCG as luteal support in GnRHa/HMG induced IVF cycles: a randomized clinical trial. Hum Reprod 11:1602–1605.
Mottla GL, Smotrich DB, Gindoff PR, Stillman RJ. (1996) Increasing clinical pregnancy rates after IVF/ET. Can immunosuppression help? J Reprod Med 41:889–891.[Web of Science][Medline]
Nugent D, Watson AJ, Killick SR, Balen AH, Rutherford AJ. (2002) A randomized controlled trial of tubal flushing with lipiodol for unexplained infertility. Fertil Steril 77:173–175.[CrossRef][Web of Science][Medline]
Ohl J, Lefebvre-Maunoury C, Wittemer C, Nisand G, Laurent MC, Hoffmann P. (2002) Nitric oxide donors for patients undergoing IVF. A prospective, double-blind, randomized, placebo-controlled trial. Hum Reprod 17:2615–2620.
Omu AE, Al Qattan F, Hamada BA. (1996) Effect of low dose continuous corticosteroid therapy in men with antisperm antibodies on spermatozoal quality and conception rate. Eur J Obstet Gynecol Reprod Biol 69:129–134.[CrossRef][Web of Science][Medline]
Orvieto R, Kerner R, Krissi H, Ashkenazi J, Rafael ZB, Bar-Hava I. (2002) Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective, randomized study. Fertil Steril 78:1268–1271.[CrossRef][Web of Science][Medline]
Parsanezhad ME, Alborzi S, Jahromi BN. (2002a) A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level. Int J Fertil Womens Med 47:272–277.[Web of Science][Medline]
Parsanezhad ME, Motazedian S, Alborzi S, Omrani G. (2002b) Effect of high dose, short course dexamethasone in clomiphene citrate resistant women with polycystic ovary syndrome. Middle East Fertil Soc J 7:93–97.
Parsanezhad ME, Alborzi S, Motazedian S, Omrani G. (2002c) Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial. Fertil Steril 78:1001–1004.[CrossRef][Web of Science][Medline]
Patton P, Burry K, Novy M, Wolf D. (1990) A comparative evaluation of intracervical and intrauterine routes in donor therapeutic insemination. Hum Reprod 5:263–265.
Paulus WE, Zhang M, Strehler E, El Danasouri I, Sterzik K. (2002) Influence of acupuncture on the pregnancy rate in patients who undergo assisted reproduction therapy. Fertil Steril 77:721–724.[CrossRef][Web of Science][Medline]
Pistorius LR, Kruger TF, de Villiers A, van der Merwe JP. (1996) A comparative study using prepared and unprepared frozen semen for donor insemination. Arch Androl 36:81–86.[Web of Science][Medline]
Pouly JL, Bassil S, Frydman R, Hedon B, Nicollet B, Prada Y, Antoine JM, Zambrano R, Donnez J. (1996) Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone. Hum Reprod 11:2085–2089.
Prato LD, Borini A, Cattoli M, Bonu MA, Sciajno R, Flamigni C. (2002) Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with gonadotropin-releasing hormone agonist. Fertil Steril 77:956–960.[CrossRef][Web of Science][Medline]
Qasim SM, Trias A, Karacan M, Shelden R, Kemmann E. (1996) Does the absence or presence of seminal fluid matter in patients undergoing ovulation induction with intrauterine insemination. Hum Reprod 11:1008–1010.
Quinn P, Stone B, Marrs R. (1990) Suboptimal laboratory conditions can affect pregnancy outcome after embryo transfer on day 1 or 2 after insemination in vitro. Fertil Steril 53:168–170.[Web of Science][Medline]
Ransom MX, Doughman NC, Garcia AJ. (1996) Menotropins alone are superior to a clomiphene citrate and menotropin combination for superovulation induction among clomiphene citrate failures. Fertil Steril 65:1169–1174.[Web of Science][Medline]
Rein MS, Jackson KV, Sable DB, Thomas P, Hornstein MD. (1996) Dexamethasone during ovulation for in vitro fertilization: a pilot study. Hum Reprod 11:253–255.
Rickes D, Nickel I, Kropf S, Kleinstein J. (2002) Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis. Fertil Steril 78:757–762.[CrossRef][Web of Science][Medline]
Rienzi L, Ubaldi F, Iacobelli M, Ferrero S, Minasi MG, Martinez F, Tesarik J, Greco E. (2002) Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer. Hum Reprod 17:1852–1855.
Rizk B, Tan SL, Kingsland C, Steer C, Mason BA, Campbell S. (1990) Ovarian cyst aspiration and the outcome of in vitro fertilization. Fertil Steril 54:661–664.[Web of Science][Medline]
Ron El R, Herman A, Golan A, Van Der Ven H, Caspi E, Diedrich K. (1990) The comparison of early follicular and midluteal administration of long-acting gonadotropin-releasing hormone agonist. Fertil Steril 54:233–237.[Web of Science][Medline]
Scholtes MC and Zeilmaker GH. (1996) A prospective, randomized study of embryo transfer results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril 65:1245–1248.[Web of Science][Medline]
Selman HA, De Santo M, Sterzik K, Coccia E, El Danasouri I. (2002) Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality. Fertil Steril 78:1061–1067.[CrossRef][Web of Science][Medline]
Shaker AG, Zosmer A, Dean N, Bekir JS, Jacobs HS, Tan SL. (1996) Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome. Fertil Steril 65:992–996.[Web of Science][Medline]
Smith KL, Grow DR, Wiczyk HP, O’Shea DL, Arny M. (2002) Does catheter type effect pregnancy rate in intrauterine insemination cycles? J Assist Reprod Genet 19:49–52.[CrossRef][Web of Science][Medline]
Sturrock NDC, Lannon B, Fay TN. (2002) Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice. Br J Clin Pharmacol 53:469–473.[CrossRef][Web of Science][Medline]
Suganuma N, Tsukahara SI, Kitagawa T, Furuhashi M, Asada Y, Kondo I. (1996) A controlled ovarian hyperstimulation regimen involving intermittent gonadotropin administration with a ‘short’ protocol of gonadotropin releasing hormone agonist for in vitro fertilization. J Assist Reprod Genet 13:43–48.[CrossRef][Web of Science][Medline]
Suikkari A, MacLachlan V, Koistinen R, Pala M, Healy D. (1996) Double-blind placebo controlled study: human biosynthetic growth hormone for assisted reproductive technology. Fertil Steril 65:800–805.[Web of Science][Medline]
Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. (2002) Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril 78:699–704.[CrossRef][Web of Science][Medline]
Takeuchi S, Futamura N, Takubo S, Noda N, Minoura H, Toyoda N. (2002) Polycystic ovary syndrome treated with laparoscopic ovarian drilling with a harmonic scalpel. A prospective, randomized study. J Reprod Med 47:816–820.[Web of Science][Medline]
Tanbo T, Dale P, Abyholm T. (1990a) Assisted fertilization in infertile women with patent fallopian tubes: a comparison of in-vitro fertilization-gamete intra-fallopian transfer and tubal embryo stage transfer. Hum Reprod 5:266–270.
Tanbo T, Abyholm T, Bjoro T, Dale P. (1990b) Ovarian stimulation in previous failures from in vitro fertilization: distinction of two groups of poor responders. Hum Reprod 5:811–815.
Tanbo T, Dale P, Kjekshus EHE, Abyholm T. (1990c) Stimulation with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression in polycystic ovarian syndrome. Fertil Steril 53:798–803.[Web of Science][Medline]
Tesarik J and Mendoza C. (2002) Effects of exogenous LH administration during ovarian stimulation of pituitary down-regulated young oocyte donors on oocyte yield and developmental competence. Hum Reprod 17:3129–3137.
Thornton S, Pantos C, Speirs A, Johnston I. (1990) Human chorionic gonadotropins to oocyte retrieval interval in in vitro fertilization – how critical is it? Fertil Steril 53:177–179.[Web of Science][Medline]
Tucker MJ, Morton PC, Wright G, Ingargiola PE, Sweitzer CL, Elsner CW, Mitchell-Leef DE, Massey JB. (1996) Enhancement of outcome from intracytoplasmic sperm injection: does co-culture or assisted hatching improve implantation rates? Hum Reprod 11:2434–2437.
Ubaldi F, Rienzi L, Ferrero S, Anniballo R, Iacobelli M, Cobellis L, Greco E. (2002) Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates. Hum Reprod 17:1544–1547.
Urbancsek J and Witthaus E. (1996) Midluteal buserelin is superior to early follicular phase buserelin in combined gonadotropin-releasing hormone analog and gonadotropin stimulation in in vitro fertilization. Fertil Steril 65:966–971.[Web of Science][Medline]
Urman B, Balaban B, Alatas C, Aksoy S, Mumcu A, Isiklar A. (2002) Zona-intact versus zona-free blastocyst transfer: a prospective, randomized study. Fertil Steril 78:392–396.[CrossRef][Web of Science][Medline]
Utsunomiya T, Naitou T, Nagaki M. (2002) A prospective trial of blastocyst culture and transfer. Hum Reprod 17:1846–1851.
Van De Helder A, Helmerhorst F, Blankhart A, Brand R, Waegemaekers C, Naaktgeboren N. (1990) Comparison of ovarian stimulation regimens for in vitro fertilisation (IVF) with and without a gonadotropin-releasing hormone (GnRH) agonist: results of a randomised study. J In Vitro Fert Embryo Transf 7:358–362.[CrossRef][Web of Science][Medline]
Van Der Auwera I, Debrock S, Spiessens C, Afschrift H, Bakelants E, Meuleman C, Meeuwis L, D’Hooghe TM. (2002) A prospective randomized study: day 2 versus day 5 embryo transfer. Hum Reprod 17:1507–1512.
Wang HS and Soong YK. (1996) Transvaginal progesterone supplementation increases serum insulin-like growth factor-binding protein-1 levels. Gynecol Endocrinol 10:349–355.[Web of Science][Medline]
Wang WH, Meng L, Hackett RJ, Oldenbourg R, Keefe DL. (2002) Rigorous thermal control during intracytoplasmic sperm injection stabilizes the meiotic spindle and improves fertilization and pregnancy rates. Fertil Steril 77:1274–1277.[CrossRef][Web of Science][Medline]
van Weering HG, Schats R, McDonnell J, Vink JM, Vermeiden JP, Hompes PG. (2002) The impact of the embryo transfer catheter on the pregnancy rate in IVF. Hum Reprod 17:666–670.
Weigert M, Krischker U, Pohl M, Poschalko G, Kindermann C, Feichtinger W. (2002) Comparison of stimulation with clomiphene citrate in combination with recombinant follicle-stimulating hormone and recombinant luteinizing hormone to stimulation with a gonadotropin-releasing hormone agonist protocol: a prospective, randomized study. Fertil Steril 78:34–39.[CrossRef][Web of Science][Medline]
Westerguard LG, Erb K, Laursen S, Rasmussen PE, Rex S. (1996) The effect of human menopausal gonadotrophin and highly purified urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down regulated normogonadotrophic woman. Hum Reprod 11:1209–1213.
Wong YF, Loong EP, Mao KR, Tam PP, Panesar NS, Neale E, Chang AM. (1990) Salivary oestradiol and progesterone after in vitro fertilization and embryo transfer using different luteal support regimens. Reprod Fertil Dev 2:351–358.[CrossRef][Medline]
Yamamoto M, Hibi H, Hirata Y, Miyake K, Ishigaki T. (1996a) Effect of varicocelectomy on sperm parameters and pregnancy rate in patients with subclinical varicocele: a randomized prospective controlled study. J Urol 155:1636–1638.[CrossRef][Web of Science][Medline]
Yamamoto M, Hibi H, Miyake K, Asada Y, Suganuma N, Tomoda Y. (1996b) Microsurgical epididymal sperm aspiration versus epididymal micropuncture with perivascular nerve stimulation for intracytoplasmic sperm injection to treat unreconstructable obstructive azoospermia. Arch Androl 36:217–224.[Web of Science][Medline]
Yang T, Tsan S, Wang B, Chang S, Ng H. (1996) The evaluation of a new 7-day gonadotropin-releasing hormone agonist protocol in the controlled ovarian hyperstimulation for in vitro fertilization. J Obstet Gynaecol Res 22:133–137.[Medline]
Yarali H, Yildiz BO, Demirol A, Zeyneloglu HB, Yigit N, Bukulmez O, Koray Z. (2002) Co-administration of metformin during rFSH treatment in patients with clomiphene citrate–resistant polycystic ovarian syndrome: a prospective randomized trial. Hum Reprod 17:289–294.
Yeung WS, Lau EY, Chan ST, Ho PC. (1996) Coculture with homologous oviductal cells improved the implantation of human embryos – a prospective randomized control trial. J Assist Reprod Genet 13:762–767.[CrossRef][Web of Science][Medline]
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
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The authors acknowledge the help of Michelle Proctor and Lisa McComb-Williams from the Cochrane MDSG base in Auckland, New Zealand, in accessing the trial database. This work has been funded by a Wellbeing of Women (RCOG) grant.
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TopAbstractIntroductionMaterials and methodsResultsDiscussionConflicts of interestAppendix 1. Included studiesAcknowledgementsReferences |
|---|
Altman DG. (1994) The scandal of poor medical research. BMJ 308:283–284.
Altman DG and Bland JM. (1997) Statistics notes: units of analysis. BMJ 314:1874.
Altman DG and Doré CJ. (1990) Randomisation and baseline comparisons in clinical trials. Lancet 335:149–153.[CrossRef][Web of Science][Medline]
Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gøtzsche PC, Lang T. (2001) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 134:663–694.
Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I, Pitkin R, Rennie D, Schulz KF, Simel D, et al. (1996) Improving the quality of reporting of randomized controlled trials – The CONSORT statement. JAMA 276:637–639.
Blomquist N. (1985) On the choice of computational unit in statistical analysis. J Clin Periodontol 12:873–876.[CrossRef][Web of Science][Medline]
Chan A-W and Altman DG. (2005) Epidemiology and reporting of randomised trials published in PubMed journals. Lancet 365:1159–1162.[CrossRef][Web of Science][Medline]
Cohlen BJ, te Velde ER, Looman CWN, Eijckemans R, Habbema JDF. (2004) Crossover or parallel design in infertility trials? The discussion continues. Fertil Steril 70:40–45.
Daya S. (1993) Is there a place for the crossover design in infertility trials? Fertil Steril 59:6–7.[Web of Science][Medline]
Daya S. (2003) Pitfalls in the design and analysis of efficacy trials in subfertility. Hum Reprod 18:1005–1009.
Devereaux PJ, Manns BJ, Ghali WA, Quan H, Guyatt GH. (2002) The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist. Control Clin Trials 23:380–388.[CrossRef][Web of Science][Medline]
Eijckemans M, Habbema JDF, te Velde ER. (2002) The analysis of crossover trials for infertility treatment. ISCB 23rd Annual Conference, Dijon, France.
Hahn S, Williamson PR, Hutton JL, Garner P, Flynn EV. (2000) Assessing the potential for bias in meta-analysis due to selective reporting of subgroup analyses within studies. Stat Med 19:3325–3336.[CrossRef][Web of Science][Medline]
Hahn S, Williamson PR, Hutton JL. (2002) Investigation of within-study selective reporting in clinical research: follow-up of applications submitted to a local research ethics committee. J Eval Clin Pract 8:353–359.[CrossRef][Web of Science][Medline]
Higgins JPT. (2005) Assessment of Study Quality. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005], section 6. In The Cochrane Library, issue 3. (John Wiley & Sons LtdIn Green S (Ed.). , Chichester, UK.).
Hill CL, LaValley MP, Felson D. (2002) Discrepancy between published report and actual conduct of randomized clinical trials. J Clin Epidemiol 55:783–786.[CrossRef][Web of Science][Medline]
Kjaergard LL, Nikolova D, Gluud C. (1999) Randomized clinical trials in hepatology: predictors of quality. Hepatology 30:1134–1138.[CrossRef][Web of Science][Medline]
McDonnell J, Goverde AJ, Vermeiden JPW. (2004) The place of the crossover design in infertility trials: a maximum likelihood approach. Hum Reprod 19:2537–2544.
Moher D, Jones A, Lepage L. (2001a) Use of the CONSORT statement and quality of reports of randomized trials: a comparative before-and-after evaluation. JAMA 285:1992–1995 for the CONSORT Group.
Moher D, Schultz KF, Altman DG. (2001b) The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomised trials. Lancet 357:1191–1194.[CrossRef][Web of Science][Medline]
Newcombe RG and Duff GR. (1987) Eyes or patients? Traps for the unwary in the statistical analysis of ophthalmological studies. Br J Ophthalmol 71:645–646.
Norman GR and Daya S. (2004) The alternating-sequence design (or multiple period crossover) trial for evaluating treatment efficacy in infertility. Fertil Steril 74:319–324.[CrossRef]
Schulz KF, Chalmers I, Grimes DA, Altman DG. (1994) Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology journals. JAMA 272:125–128.
Schulz KF, Chalmers I, Hayes RJ, Altman DG. (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273:408–412.
Schulz KF, Grimes DA, Altman DG, Hayes RJ. (1996) Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology. BMJ 312:742–744.
Senn S. (1993) Cross-Over Trials in Clinical Research(Wiley, Chichester, UK.).
US Cochrane Center. (2004) Master list of journals being searched. http://www.cochrane.us/masterlist.asp.
Vail A and Gardener E. (2003) Common statistical errors in the design and analysis of subfertility trials. Hum Reprod 18:1000–1004.
Vandekerckhove P, O’Donovan PA, Lilford RJ, Harada TW. (1993) Infertility treatment: from cookery to science. The epidemiology of randomised controlled trials. BJOG 100:1005–1036.[CrossRef]
Submitted on March 27, 2006; resubmitted on May 15, 2006; accepted on May 19, 2006.
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