The Experts below are selected from a list of 4416 Experts worldwide ranked by ideXlab platform

Cindy Farquhar - One of the best experts on this subject based on the ideXlab platform.

  • Intrauterine Insemination versus fallopian tube sperm perfusion for non tubal infertility
    Cochrane Database of Systematic Reviews, 2013
    Co-Authors: Astrid E P Cantineau, Maas Jan Heineman, Ben J Cohlen, Jane Marjoribanks, Cindy Farquhar
    Abstract:

    Background Intrauterine Insemination (IUI) is a common treatment for couples with subfertility that does not involve the fallopian tubes. It is used to bring the sperm close to the released oocyte. Another method of introducing sperm is fallopian tube sperm perfusion (FSP). Fallopian tube sperm perfusion ensures the presence of higher sperm densities in the fallopian tubes at the time of ovulation than does standard IUI. These treatments are often used in combination with ovarian hyperstimulation. Objectives To compare Intrauterine Insemination versus fallopian tube sperm perfusion in the treatment of non-tubal subfertility, for live birth and pregnancy outcomes. Search methods We searched the Menstrual Disorders and Subfertility Group Trials Register, MEDLINE, CINAHL and EMBASE from inception to September 2013. We also searched study reference lists and trial registers. Selection criteria Randomised controlled trials (RCTs) comparing IUI with FSP in couples with non-tubal subfertility were included. Data collection and analysis Two review authors independently selected studies for inclusion, assessed study quality and extracted the data. If studies were sufficiently similar, data were combined using a fixed-effect model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). A random-effects model was used if substantial statistical heterogeneity was detected. Studies that included participants with unexplained or mixed (non-tubal) subfertility were analysed separately from studies restricted to participants with mild or moderate male factor subfertility. The overall quality of evidence for the main outcomes was summarised using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Main results The review included 16 RCTs. Fourteen RCTs (1745 women) were included in the meta-analysis. Only three studies reported live birth per couple. No evidence of a statistically significant difference was noted between IUI and FSP in live birth (OR 0.94, 95% CI 0.59 to 1.49, three RCTs, 633 women, I-2 = 0%, low-quality evidence) or clinical pregnancy (OR 0.75, 95% CI 0.49 to 1.12, 14 RCTs, 1745 women, I-2 = 52%, low-quality evidence). These findings suggest that for a couple with a 13% chance of live birth using FSP, the chance when using IUI will be between 8% and 19%; and that for a couple with a 19% chance of pregnancy using FSP, the chance of pregnancy when using IUI will be between 10% and 20%. Nor was evidence found of a statistically significant difference between IUI and FSP in per-pregnancy of multiple pregnancy (OR 0.96, 95% CI 0.44 to 2.07, eight RCTs, 197 women, I-2 = 0%, low-quality evidence), miscarriage (OR 1.23, 95% CI 0.60 to 2.53, seven RCTs, 199 women, I-2 = 0%, low-quality evidence) or ectopic pregnancy (OR 1.71, 95% CI 0.42 to 6.88, four RCTs, 111 women, I-2 = 0%, very low quality evidence). Substantial heterogeneity was noted for the outcome of clinical pregnancy (I-2 = 54%), for which no clear explanation was provided. Authors' conclusions Currently no clear evidence suggests any difference between IUI and FSP with respect to their effectiveness and safety for treating couples with non-tubal subfertility. However, a high level of uncertainty is evident in the findings, and additional research may be useful.

  • semen preparation techniques for Intrauterine Insemination
    Cochrane Database of Systematic Reviews, 2007
    Co-Authors: Carolien M Boomsma, Maas Jan Heineman, Ben J Cohlen, Cindy Farquhar
    Abstract:

    Background Semen preparation techniques for assisted reproduction, including Intrauterine Insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa as possible might influence treatment choices and therefore outcomes. Objectives To compare the effectiveness of gradient, swim-up, or wash and centrifugation semen preparation techniques on clinical outcome in subfertile couples undergoing Intrauterine Insemination (IUI). Search strategy We searched the Menstrual Disorders and Subfertility Group Trials Register (3 January 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to January 2007), EMBASE (1980 to January 2007), Science Direct Database (1966 to January 2007), National Research Register (2000 to 2007), Biological Abstracts (2000 to January 2007), CINAHL (1982 to October 2006) and reference lists of relevant articles. We also contacted experts and authors in the field. Selection criteria Parallel randomized controlled trials (RCTs) comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI in terms of clinical outcome were included. Data collection and analysis Two reviewer authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Main results Five RCTs, including 262 couples in total, were included in the meta-analysis (Dodson 1998; Grigoriou 2005; Posada 2005; Soliman 2005; Xu 2000). Xu compared the three techniques; Soliman compared a gradient technique versus a wash technique; Dodson and Posada compared a gradient technique versus a swim-up technique; whereas Grigoriou compared swim-up versus a wash technique. No trials reported the primary outcome of live birth. There was no evidence of a difference between pregnancy rates (PR) for swim-up versus a gradient or wash and centrifugation technique (Peto OR 1.57, 95% CI 0.74 to 3.32; Peto OR 0.41, 95% CI 0.15 to 1.10, respectively); nor in the two studies comparing a gradient technique versus wash and centrifugation (Peto OR 1.76, 95% CI 0.57 to 5.44). There was no evidence of a difference in them is carriage rate (MR) in two studies comparing swim- up versus a gradient technique (Peto OR 0.13, 95% CI 0.01 to 1.33). Authors' conclusions There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/or a swim-up and/or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted.

  • semen preparation techniques for Intrauterine Insemination
    Cochrane Database of Systematic Reviews, 2007
    Co-Authors: Carolien M Boomsma, Maas Jan Heineman, Ben J Cohlen, Cindy Farquhar
    Abstract:

    BACKGROUND: Semen preparation techniques for assisted reproduction, including Intrauterine Insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa might influence treatment choices and therefore outcomes. OBJECTIVES: To compare the effectiveness of gradient, swim-up, or wash and centrifugation in subfertile couples undergoing Intrauterine Insemination (IUI) on clinical outcome as well as on semen parameters. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group's trials register (30 June 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), Science Direct Database (1966 to July 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), National Research Register (2000 to Issue 2, 2003), Biological Abstracts (2000 to June 2003), CINAHL (1982 to July 2003) and reference lists of relevant articles. We also contacted experts and authors in the field. SELECTION CRITERIA: Parallel randomised controlled trials (RCTs), comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI, were included. RCTs or split sample studies examining semen parameters after different semen preparation techniques were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Two randomised controlled trials comparing clinical outcomes, including 81 participants in total, were included in the meta-analysis (Dodson 1998-I/ II; Xu 2000-I/ II). Both studies compared swim-up technique versus gradient technique in 65 subfertile couples undergoing IUI. One study compared the effectiveness of both techniques with wash technique. No trials reported the primary outcome of live birth. There was no statistically significant difference between pregnancy rates (PR) for swim-up versus gradient / wash centrifuge (Peto OR 0.55, 95% CI 0.17 to 1.76; Peto OR 1.74, 95% CI 0.2 to 14.9; PR/ couple swim-up 20%, gradient 40%, wash 12.5%) or gradient versus wash centrifuge (Peto OR 4.01, 95% CI 0.82 to 19.56; PR/ couple swim-up 15%, gradient 20%). There was no significant difference in the miscarriage rate (MR) per couple between either of the three treatment groups in the one trial reporting this outcome (MR/ couple swim-up 0%, gradient 10.3%, wash 0%. MR/ pregnancy gradient 30.3%). There was no statistically significant difference in the multiple pregnancy rate (MPR) per couple between either of the three treatment groups in Dodson 1998-I/ II (MPR/ couple swim -up 0%, gradient 0%, wash 6.3%). One triplet pregnancy was recorded. Fifteen studies comparing semen parameters after processing were included. Two studies were included in the meta-analysis, we were not able to pool results. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/ or a swim-up and/ or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted. Results from studies comparing semen parameters may suggest a preference for gradient technique, but firm conclusions cannot be drawn and the limitations should be taken into consideration

Ahmed Sayed - One of the best experts on this subject based on the ideXlab platform.

  • extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing Intrauterine Insemination a randomized controlled trial
    Reproductive Biology and Endocrinology, 2011
    Co-Authors: Usama M Fouda, Ahmed Sayed
    Abstract:

    Background: The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and Intrauterine Insemination (IUI). Methods: Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine Insemination was performed 36 to 40 hours after HCG administration. Results: Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). Conclusion: The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. Trial registration: ClinicalTrials.gov, NCT01232075

  • extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing Intrauterine Insemination a randomized controlled trial
    Reproductive Biology and Endocrinology, 2011
    Co-Authors: Usama M Fouda, Ahmed Sayed
    Abstract:

    The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and Intrauterine Insemination (IUI). Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine Insemination was performed 36 to 40 hours after HCG administration. Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. ClinicalTrials.gov, NCT01232075

Tomomoto Ishikawa - One of the best experts on this subject based on the ideXlab platform.

  • minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or Intrauterine Insemination without a human menopausal gonadotropin
    BMC Research Notes, 2018
    Co-Authors: Yukiko Takaya, Hidehiko Matsubayashi, Kotaro Kitaya, Rie Nishiyama, Kohei Yamaguchi, Takumi Takeuchi, Tomomoto Ishikawa
    Abstract:

    The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or Intrauterine Insemination without a human menopausal gonadotropin stimulation. We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and 162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup analyses showed slight differences among the four groups, which may have been due to the ovarian function of each group. Miscarriage was not related to progesterone and estradiol concentrations. These values may be useful for the evaluation of necessary values for pregnancy with timed intercourse or Intrauterine Insemination.

  • Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or Intrauterine Insemination without a human menopausal gonadotropin
    BMC, 2018
    Co-Authors: Yukiko Takaya, Hidehiko Matsubayashi, Kotaro Kitaya, Rie Nishiyama, Kohei Yamaguchi, Takumi Takeuchi, Tomomoto Ishikawa
    Abstract:

    Abstract Objective The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or Intrauterine Insemination without a human menopausal gonadotropin stimulation. Results We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P 

Hannu Martikainen - One of the best experts on this subject based on the ideXlab platform.

  • improved pregnancy rate with administration of hcg after Intrauterine Insemination a pilot study
    Reproductive Biology and Endocrinology, 2010
    Co-Authors: Ilkka Y Jarvela, Juha S Tapanainen, Hannu Martikainen
    Abstract:

    In natural cycles, women conceive when intercourse takes place during a six-day period ending on the day of ovulation. The current practice in Intrauterine Insemination (IUI) cycles is to perform the IUI 24-36 hours after the hCG administration, when the ovulation is already imminent. In this study hCG was administered after the IUI, which more closely resembles the fertilisation process in natural cycles. All the IUIs performed since the beginning of 2007 were analysed retrospectively. Our standard protocol has been to perform the IUI 24-32 hours after hCG administration. From the end of 2008, we started to inject hCG after the IUI at random. The main outcome measure was the result of a urinary pregnancy test. Generalized Estimating Equations (GEE) was used to identify independent factors affecting the cycle outcome. The analysis included 228 cycles with hCG administered before and 104 cycles hCG administered after the IUI. The pregnancy rates were 10.9% and 19.6% (P = 0.040), respectively. Independent factors (OR, 95% CI) affecting the cycle outcome were sperm count (2.65, 1.20-5.81), number of follicles > 16 mm at IUI (2.01, 1.07-3.81) and the time of hCG administration (2.21, 1.16-4.19). Improved pregnancy rate was observed with administration of hCG after IUI.

  • Intrauterine Insemination treatment in subfertility an analysis of factors affecting outcome
    Human Reproduction, 1999
    Co-Authors: Sinikka Nuojuahuttunen, Candido Tomas, Risto Bloigu, Leena Tuomivaara, Hannu Martikainen
    Abstract:

    : A total of 811 Intrauterine Insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis.

Carolien M Boomsma - One of the best experts on this subject based on the ideXlab platform.

  • semen preparation techniques for Intrauterine Insemination
    Cochrane Database of Systematic Reviews, 2007
    Co-Authors: Carolien M Boomsma, Maas Jan Heineman, Ben J Cohlen, Cindy Farquhar
    Abstract:

    Background Semen preparation techniques for assisted reproduction, including Intrauterine Insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa as possible might influence treatment choices and therefore outcomes. Objectives To compare the effectiveness of gradient, swim-up, or wash and centrifugation semen preparation techniques on clinical outcome in subfertile couples undergoing Intrauterine Insemination (IUI). Search strategy We searched the Menstrual Disorders and Subfertility Group Trials Register (3 January 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to January 2007), EMBASE (1980 to January 2007), Science Direct Database (1966 to January 2007), National Research Register (2000 to 2007), Biological Abstracts (2000 to January 2007), CINAHL (1982 to October 2006) and reference lists of relevant articles. We also contacted experts and authors in the field. Selection criteria Parallel randomized controlled trials (RCTs) comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI in terms of clinical outcome were included. Data collection and analysis Two reviewer authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Main results Five RCTs, including 262 couples in total, were included in the meta-analysis (Dodson 1998; Grigoriou 2005; Posada 2005; Soliman 2005; Xu 2000). Xu compared the three techniques; Soliman compared a gradient technique versus a wash technique; Dodson and Posada compared a gradient technique versus a swim-up technique; whereas Grigoriou compared swim-up versus a wash technique. No trials reported the primary outcome of live birth. There was no evidence of a difference between pregnancy rates (PR) for swim-up versus a gradient or wash and centrifugation technique (Peto OR 1.57, 95% CI 0.74 to 3.32; Peto OR 0.41, 95% CI 0.15 to 1.10, respectively); nor in the two studies comparing a gradient technique versus wash and centrifugation (Peto OR 1.76, 95% CI 0.57 to 5.44). There was no evidence of a difference in them is carriage rate (MR) in two studies comparing swim- up versus a gradient technique (Peto OR 0.13, 95% CI 0.01 to 1.33). Authors' conclusions There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/or a swim-up and/or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted.

  • semen preparation techniques for Intrauterine Insemination
    Cochrane Database of Systematic Reviews, 2007
    Co-Authors: Carolien M Boomsma, Maas Jan Heineman, Ben J Cohlen, Cindy Farquhar
    Abstract:

    BACKGROUND: Semen preparation techniques for assisted reproduction, including Intrauterine Insemination (IUI), were developed to separate the motile morphological normal spermatozoa. Leucocytes, bacteria and dead spermatozoa produce oxygen radicals that negatively influence the ability to fertilize the egg. The yield of as many motile, morphologically normal spermatozoa might influence treatment choices and therefore outcomes. OBJECTIVES: To compare the effectiveness of gradient, swim-up, or wash and centrifugation in subfertile couples undergoing Intrauterine Insemination (IUI) on clinical outcome as well as on semen parameters. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group's trials register (30 June 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), Science Direct Database (1966 to July 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), National Research Register (2000 to Issue 2, 2003), Biological Abstracts (2000 to June 2003), CINAHL (1982 to July 2003) and reference lists of relevant articles. We also contacted experts and authors in the field. SELECTION CRITERIA: Parallel randomised controlled trials (RCTs), comparing the efficacy of semen preparation techniques used for subfertile couples undergoing IUI, were included. RCTs or split sample studies examining semen parameters after different semen preparation techniques were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Two randomised controlled trials comparing clinical outcomes, including 81 participants in total, were included in the meta-analysis (Dodson 1998-I/ II; Xu 2000-I/ II). Both studies compared swim-up technique versus gradient technique in 65 subfertile couples undergoing IUI. One study compared the effectiveness of both techniques with wash technique. No trials reported the primary outcome of live birth. There was no statistically significant difference between pregnancy rates (PR) for swim-up versus gradient / wash centrifuge (Peto OR 0.55, 95% CI 0.17 to 1.76; Peto OR 1.74, 95% CI 0.2 to 14.9; PR/ couple swim-up 20%, gradient 40%, wash 12.5%) or gradient versus wash centrifuge (Peto OR 4.01, 95% CI 0.82 to 19.56; PR/ couple swim-up 15%, gradient 20%). There was no significant difference in the miscarriage rate (MR) per couple between either of the three treatment groups in the one trial reporting this outcome (MR/ couple swim-up 0%, gradient 10.3%, wash 0%. MR/ pregnancy gradient 30.3%). There was no statistically significant difference in the multiple pregnancy rate (MPR) per couple between either of the three treatment groups in Dodson 1998-I/ II (MPR/ couple swim -up 0%, gradient 0%, wash 6.3%). One triplet pregnancy was recorded. Fifteen studies comparing semen parameters after processing were included. Two studies were included in the meta-analysis, we were not able to pool results. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend any specific preparation technique. Large high quality randomised controlled trials, comparing the effectiveness of a gradient and/ or a swim-up and/ or wash and centrifugation technique on clinical outcome are lacking. Further randomised trials are warranted. Results from studies comparing semen parameters may suggest a preference for gradient technique, but firm conclusions cannot be drawn and the limitations should be taken into consideration