Home About us Editorial board Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 216
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 27  |  Issue : 3  |  Page : 171-176

Comparison of clinical efficacy of long- versus short-acting gonadotrophin-releasing hormone agonists for pituitary down regulation in In vitro fertilisation cycles


1 Department of Obstetrics and Gynaecology, National Hospital Abuja, Abuja, Nigeria
2 Department of Chemical Pathology, National Hospital Abuja, Abuja, Nigeria
3 Department of Obstetrics and Gynaecology, Faculty of Medicine, Nnamdi Azikiwe University, Nnewi Campus, Nigeria

Date of Submission02-Apr-2020
Date of Decision22-Apr-2020
Date of Acceptance11-Jun-2020
Date of Web Publication17-Jul-2020

Correspondence Address:
Dr. Maureen Uche Umemmuo
Department of Obstetrics and Gynaecology, National Hospital Abuja, Abuja
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_65_20

Rights and Permissions
  Abstract 


Background: Gonadotrophin-Releasing Hormone agonist (GnRHa) – long and short acting – is used for pituitary down regulation prior to ovarian stimulation in in vitro fertilisation (IVF) treatment. However, there are controversies in the literature as to their effectiveness, dose of gonadotrophin needed subsequently for ovarian stimulation and the clinical outcome. Objective: The objective of the study was to compare the efficacy of single-dose long-acting GnRHa – goserelin – and daily dose short-acting GnRHa – buserelin – for pituitary down regulation and their clinical outcome in IVF treatment. Materials and Methods: This prospective comparative study was undertaken at the IVF centre in National Hospital Abuja, a public tertiary hospital in Nigeria. A total of 114 IVF patients were consecutively allocated into either long-acting GnRHa – goserelin – 3.6 mg single dose (Group A) or short-acting GnRHa – buserelin – 0.5 mg daily (Group B) both starting on day 21 of the cycle preceding the IVF treatment. The effects on pituitary down regulation and treatment outcomes were compared. Results: Time taken (days) to achieve down regulation (22.6 ± 4.3 vs. 26.1 ± 8.0; P = 0.084) and the mean number of human menopausal gonadotrophin (HMG) doses used (57.7 ± 13.7 vs. 54.2 ± 16.7; P = 0.222) were similar in the two groups. Although the number of oocytes retrieved (9.9 ± 6.7 vs. 7.2 ± 5.0; P = 0.02) and fertilised (6.2 ± 4.4 vs. 4.6 ± 3.5; P = 0.04) were significantly higher in Group A, there was no statistically significant difference in the number of embryos (4.4 ± 2.6 vs. 4.0 ± 3.0; P = 0.850) and clinical pregnancy rate at 6 weeks (49.2% vs. 43.6%; odds ratio 1.249; confidence interval = 0.579–2.612; P = 0.578) in both the groups. While group B had a significantly higher number of hospital visits (P = 0.0001) as well as a higher number of injections (P = 0.0001), the mean cost of GnRHa and gonadotrophin used was significantly higher in Group A (P = 0.043). Conclusion: Single-dose long-acting GnRHa is as effective as daily dose short-acting GnRHa for pituitary desensitisation prior to controlled ovarian stimulation in IVF cycles.

Keywords: Controlled ovarian stimulation, down regulation, gonadotrophin-releasing hormone agonist, in vitro fertilisation


How to cite this article:
Umemmuo MU, Efetie ER, Agboghoroma CO, Momoh JA, Ikechebelu JI. Comparison of clinical efficacy of long- versus short-acting gonadotrophin-releasing hormone agonists for pituitary down regulation in In vitro fertilisation cycles. Niger Postgrad Med J 2020;27:171-6

How to cite this URL:
Umemmuo MU, Efetie ER, Agboghoroma CO, Momoh JA, Ikechebelu JI. Comparison of clinical efficacy of long- versus short-acting gonadotrophin-releasing hormone agonists for pituitary down regulation in In vitro fertilisation cycles. Niger Postgrad Med J [serial online] 2020 [cited 2020 Sep 23];27:171-6. Available from: http://www.npmj.org/text.asp?2020/27/3/171/289918




  Introduction Top


Ovulation induction is regarded as the key step inin vitro fertilisation (IVF) treatment. Over the years, efforts were made to simplify and improve the outcome of ovulation induction. Gonadotrophin-releasing hormone agonist (GnRHa) usage in controlled ovarian stimulation in IVF treatment marked a major advancement in the field of Assisted Reproductive Technology (ART).[1]

GnRHa causes pituitary desensitisation and enhances gonadotrophin efficacy. The use of GnRHa is associated with the prevention of premature luteinising hormone (LH) surge and endogenous luteinisation and avoidance of cancellation of cycles.[2],[3],[4] It leads to an increase in the number of follicles, synchronisation of follicular growth and better scheduling of the treatment cycles. It also contributes to improvement in endometrial receptivity and widening implantation window. Overall, the use of GnRHa in IVF cycles gives higher pregnancy rates.[5],[6],[7]

The GnRHa long protocol which entails commencement of downregulation in the early follicular or mid-luteal period of the cycle preceding the IVF treatment is the most commonly practised and it is associated with good results.[8],[9],[10] Both short- and long-acting forms of GnRH agonist are used in clinical practice. The daily dose short-acting form given as a subcutaneous injection or intranasal spray is not convenient and it is stressful. The single depot injection long-acting form is associated with better convenience, good compliance, reduced stress and cost-effective.[11] However, there are concerns of the potential for prolonged pituitary suppression and the need for higher doses and longer duration of gonadotrophin use for ovarian stimulation.

There are controversies in the literature as to the most effective and acceptable preparation for use in GnRHa long protocol ovarian stimulation in IVF treatment.[12],[13],[14] This study aims to compare the efficacy of a single dose of long-acting GnRHa – goserelin – with daily doses of short-acting GnRHa – buserelin – on pituitary down regulation and clinical outcome in IVF cycles. To the best our knowledge, this is the first time this study has been carried out in Nigeria.


  Materials and Methods Top


Ethical clearancez

The study was approved by the Ethical Review Committee (ERC) of National Hospital Abuja, with ERC assigned number NHA/EC/029/2014 on February 13, 2015.

Study design

This was a prospective comparative study of two methods of downregulation in IVF treatment cycles done in the IVF Centre, of National Hospital Abuja, a public tertiary hospital, between February 2015 and January 2016. All the participants were made to sign informed consent.

Determination of sample size

The formula for comparison of groups was used in the determination of the sample size (n).[15]



n = sample size; P1 and P2 = prevalence or proportion of the attribute present in Groups A and B, respectively; P1 = 72.7% and P2 = 53.6% (clinical pregnancy rate in Groups A and B, respectively)[16]Za and ZB = standard normal deviate corresponding to level of significance and 1 minus power respectively. At 95% confidence level, with 80% power, Za = 1.96 and ZB = 0.84.

n = 6. 1 which is approximately 97

The minimum sample size for the two groups was 97. Ten percent (10%) was added to take care of the ones that may fail downregulation or any other attrition. The final total minimum sample size was 106 and was divided into 53 for each group. The ones on long-acting GnRHa (goserelin) were categorised as Group A, while the ones on short-acting GnRHa (buserelin) were categorised as Group B.

Patient recruitment

The patients were recruited consecutively into the two arms of the study after adequate counselling. They were educated on the two drugs and their method of administration, and there was no extra cost implication on the IVF fee for use of any of the two drugs. Emphasis was on the fact that both the drugs were approved and safe. Since the IVF treatment was fully paid by the patients, selection into either of the group was partly influenced by the patient's choice. Patients who did not indicate any preference were matched for the age before allotment to a group. This is to ensure that both the treatment groups were matched for age.

The inclusion criteria were women aged <40 years, not more than three previous IVF-ET attempts, basal serum follicle-stimulating hormone (FSH) concentration <10 mIU/mL on day 3 of the menstrual cycle and no history of gonadotrophin use within 3 months preceding the study. The exclusion criteria were moderate-to-severe endometriosis, male factor infertility, use of donated gamete and previous ovarian surgery.

Down regulation; gonadotrophin-releasing hormone agonist regimen

After obtaining the patient's consent, a venous blood sample was taken from each patient for serum concentration of LH, FSH and oestradiol between day 2 and 5 of menstrual cycle. A baseline transvaginal scan was also done before the commencement of the GnRHa administration on day 21 of the menstrual cycle. In the long-acting GnRHa group (Group A), patients received a subcutaneous single dose of 3.6 mg of goserelin acetate (Zoladex® depot, AstraZeneca Ltd., Kings Langley, U.K.). In the short-acting GnRHa group (Group B), patients received a subcutaneous daily dose of 0.5 mg of buserelin acetate (Superfact®, Hoechst AG, Frankfurt, Germany) at the hospital until ovarian suppression is confirmed. Transvaginal ultrasound, FSH and oestradiol were done on day 14 for both the groups. Patients were considered to have downregulated when an ultrasound scan confirmed an endometrial thickness <3 mm or FSH level below 4 mIU/L and oestradiol level below 50 pgm/ml. If not yet downregulated on day 14, the scan will be repeated a week later to confirm downregulation before the commencement of stimulation.

Stimulation

Multiple follicular stimulation was achieved with human menopausal gonadotrophin (Diclair-HP HMG, R Germany, or Menogon, Germany R). A sliding scale regimen based on the age of the patient was used for human menopausal gonadotrophin administration. Women <34 years of age received 225 IU daily; 35–38 years, 300 IU daily; and > 38 years, 450 IU daily. Follicular development was monitored with transvaginal ultrasonography (SonoAceR7, Sansung Medison) done on day 6 of gonadotrophin stimulation and follow-up on day 8. The mean maximal follicular diameter was obtained from measuring the leading follicle in two planes at 90° to each other. The 10,000 IU of human chorionic gonadotrophin (HCG) (Pregnyl®, Organon, The Netherlands) was administered when the leading follicle is at least 18 mm in mean diameter, and at least two follicles are larger than 16 mm. If the above-described criteria are not met by the follicular measurements, then a further scan was performed after 48 h, or a projected follicular growth of ~2 mm/day was employed to estimate the time of HCG injection. Transvaginal ultrasound guided-retrieval of oocytes was done 34–36 h after HCG injection with a 17-gauge aspiration needle.

In vitro fertilisation and embryo transfer

Transvaginal oocyte retrieval under ultrasound guidance was performed 36 h post HCG injection. Oocytes were aspirated into sterile Falcon round-bottom tubes (Falcon REF 352001, 14 ml) and were poured into the scanning dish (Falcon™ Tissue culture dish REF 353003). Oocytes were identified from the aspirate and placed into falcon tissue culture dish (Falcon REF 353002) containing the handling media – G-MOPS plus – which will be covered with Ovoil (Vitrolife, Sweden) placed on a heated table at 37°C. The oocytes were then washed thoroughly and placed into already equilibrated culture media – G-IVF plus – and allowed to rest between 2 and 4 h after which they will be inseminated with already prepared semen sample (approximately 200,000 spermatozoa per well). Fertilisation was checked 18–20 h post insemination, a normal fertilisation was confirmed when two polar bodies and two pronuclei were observed at 18–20 h after insemination. For fertilisation and embryo culture, a sequential media system commercially produced by Vitrolife (G-5 Series™, Vitrolife, Kungsbacka, Sweden) was used according to the manufacturer's guidance.

The cell division of the zygote was checked 24 h post fertilisation. Normal embryos on day 2 were observed to have 2–4 blastomeres. Embryo grading was done according to the criteria of Veeck by two different embryologists in a blinded manner. Embryos were graded A–C according to their quality considering the size of blastomeres, the number of blastomeres, fragmentation percentages, zona pellucida thickness and the shape of the embryo.

Embryo transfer was performed on day 2 when the embryos will be at 2–4-cell stage. Two to four embryos were transferred (depending on the age and weight of the patient) into the endometrial cavity (1–2 cm away from the fundus) using transfer catheter (Sure-pro Ultra® Embryo Replacement Catheter with Stylet, soft, 23 cm, Wallace Smith Medical international Ltd., Mexico) under ultrasound guidance.

The luteal phase support was commenced a day before oocytes retrieval and continued up to 8 weeks of gestation with progesterone PhEur (cyclogest® 400 mg, Actavis, Barnstaple, EX32 8NS, UK). Pregnancy tests were performed on day 14 post embryo transfer with both commercial pregnancy test kit and Beta HCG hormonal test. Clinical pregnancies were confirmed by transvaginal ultrasound scan at 6 week gestation.

Sample collection

A venous blood sample was taken from each patient before the commencement of the GnRHa administration and on day 14 of the downregulation. These samples were analysed for plasma concentrations of LH, FSH and oestradiol.

Plasma follicle-stimulating hormone, luteinising hormone and oestradiol determination

Blood samples obtained were centrifuged at 2600 rpm for 5 min, and sera were frozen and stored at −20°C. LH, FSH and oestradiol concentrations were measured by electrochemiluminescence immunoassay (ECLIA) (ECLIA®, Roche, USA). The assay's intra- and inter-assay coefficients of variation were given by the manufacturer as <10% and <8%, respectively, and cross-reaction with hCG was given as <0.001%. Control samples for precision and accuracy were added to each batch of the assays and all were within acceptable limits.

Statistical analysis

Information was obtained on the adequacy of pituitary suppression, number and quality of oocytes and embryo as well as clinical outcome in terms of pregnancy rate. The cost to the patient was also considered.

The statistical analysis was done using IBM SPSS Statistics for windows, Version 20.0, Armonk, NY:IBM Corp. Student's t-test (two-tailed) or the Mann–Whitney U-test (2-tailed) was used for comparison of means. Mann–Whitney U-test was used for variables that were not normally distributed and the Chi-square test and Fisher's exact test were used for proportions. P < 0.05 was considered statistically significant.


  Results Top


There was no statistically significant difference in demographic and basal endocrine level (age, duration of infertility, basal E2 and LH levels) in the two groups [Table 1].
Table 1: Basic characteristics and basal endocrine levels of patients treated with long-acting and short-acting gonadotrophin-releasing hormone agonist for pituitary down regulation in in vitro fertilisation cycles

Click here to view


[Table 2] shows that there was no statistically significant difference in the number of days for downregulation in the two groups. Down regulation of the pituitary was achieved in both groups by day 14. The levels of oestradiol and LH and endometrial thickness were not significantly different in the two groups. There was also no statistically significant difference in the mean number of HMG doses and number of stimulation days in the two groups.
Table 2: Comparison of ovarian down regulation and ovarian stimulation using human menopausal gonadotrophin in long- and short-acting gonadotrophin releasing hormone agonist groups

Click here to view


[Table 3] shows that there were a significant higher number of oocytes retrieved and fertilised in the long-acting compared to short-acting GnRHa group. However, the number of good-quality embryos obtained and transferred was not significantly different in the two groups. The clinical pregnancy rate at 6 weeks in the long-acting group was 49.2% compared to 43.6% in the short-acting group, with an odd ratio of 1.249 (confidence interval = 0.579–2.612). However, the difference did not reach a significant level (P = 0.578) [Table 4].
Table 3: Ovarian response, oocyte recovery, fertilisation and embryo transfer in long-acting and short-acting gonadotrophin-releasing hormone agonist groups

Click here to view
Table 4: Comparison of clinical pregnancy rate at 6 weeks in patients who used long-acting gonadotrophin-releasing hormone agonist and short-acting gonadotrophin-releasing hormone agonist

Click here to view


The short-acting GnRHa group had a significantly higher number of hospital visits (37.2 ± 5.8 vs. 15.4 ± 5.8, P = 0.0001) and received a higher number of injections compared to the long-acting group (37.0 ± 10.0 vs. 14.5 ± 5.9, P = 0.0001). However, the total cost (Naira) of downregulation and ovarian stimulation was significantly higher in the long-acting GnRH agonist group compared with the short-acting GnRHa group (200,983.1 ± 41,079.6 vs. 183,490.1 ± 50,238.6, P = 0.043) [Table 5].
Table 5: Comparison of number of hospital visits, number of injections, total cost of down regulation and ovarian stimulation in patients who used long-acting gonadotrophin releasing hormone agonist and those who used short acting gonadotrophin-releasing hormone agonist

Click here to view



  Discussion Top


In this study, both groups were well matched in demographic and basal endocrine levels. There was no statistically significant difference in the level of downregulation achieved on day 14 of GnRHa use in the two groups. The number of doses and days of gonadotrophin stimulation was also not significantly different. This finding is similar to some published reports.[16],[17],[18] which showed that the duration of ovarian stimulation is not prolonged by a single dose of long-acting GnRHa. However, some reports are at variance with this finding. Tapanainem et al.[19] in their study using the same drug reported that women in the goserelin group required more ampoules of gonadotrophin, though their study used intranasal buserelin instead of the subcutaneous route. Duan et al.[20] found in their study that the group using long-acting GnRHa had more profound pituitary suppression with lower serum LH concentration on day 14 of down regulation requiring higher gonadotrophin dosage and longer days of treatment. Three Cochrane reviews on the same subject concluded that that the use of long-acting GnRHa was associated with increased requirements for gonadotrophins.[12],[21],[22]

Although the number of oocytes retrieved and fertilised in the long-acting GnRHa group was significantly higher in this study, the total number of good-quality embryos generated and transferred was similar in the two groups. This is similar to the finding in a study by Tehraninejad et al.[23] but differs from the study by Geber et al.[24] where there were no differences in the number of follicles aspirated and oocytes retrieved in the two groups. In another study, the quality of oocytes retrieved and embryos generated was found to be similar in the two groups.[25]

In this study, we also accessed the pregnancy rates and found the clinical pregnancy rate (pregnancy at 6 weeks confirmed by transvaginal ultrasound) similar in the two groups. This finding corroborates many previous reports showing similar pregnancy rates between long-acting and short-acting GnRHa.[17],[20],[25] Although some researchers have documented superior pregnancy outcomes with short-acting GnRHa (buserelin) over long-acting GnRHa.[20] More researchers have reported significantly higher pregnancy rates with long-acting GnRHa than short-acting GnRHa.[25],[26],[27] Even lower doses of depot GnRHa have also been shown to produce good results.[28],[29]

In this study, patients on buserelin had a higher number of hospital visits as well as a higher number of injections. Both were significant (P < 0.001, P < 0.001 respectively). However, the cost of drugs was significantly higher in the long-acting GnRHa group. This finding is similar to the report by other researchers who showed that long-acting GnRHa increases the cost of an IVF cycle by prolonging the period of ovulation stimulation and higher doses of gonadotrophin used.[12] However, the reduced frequency of injections and hospital visits in the long-acting GnRHa group is associated with psychosocial comfort, convenience, less pain and savings in transport cost. These can serve as compensation for the higher cost of drugs. This is also important, especially in developing countries like Nigeria, where there are fewer public IVF centres, and the risks associated with transportation are enormous.

Furthermore, studies have shown that patients in IVF treatment tend to choose options with fewer injection doses. In a study by Haydardedeoǧlu and Kılıçdaǧ,[3] combination of the depot form of GnRH agonist and corifollitropin alfa was a satisfactory option for patients who could have dropped out of IVF treatment because of the fear and added stress of multiple injections.[3]

A potential limitation of this study is the nonrandomisation of patient selection because they paid for the drugs, thus had the option of choosing the drug of preference though they were matched for age.


  Conclusion Top


This study showed that a single depot long-acting GnRHa is as effective as a daily short-acting GnRHa for pituitary down regulation in IVF treatment. Their effect on pituitary down regulation, the doses and number of days of ovarian stimulation and clinical pregnancy rates are not significantly different. However, the cost of down regulation and ovarian stimulation using long-acting GnRHa – goserelin – is significantly higher than short-acting GnRHa – buserelin. It is recommended that clients should be counselled on these facts prior to down regulation. There is a need for more studies comparing the long-acting and the short-acting GnRHa, especially in Nigeria, where there is no such study before. The effects of using lower doses of long-acting GnRHa need to be further explored.

Acknowledgement

The authors wish to express appreciation to the consultants and staff of the IVF Centre, Department of Obstetrics and Gynaecology, National Hospital Abuja, for their inputs and services rendered to patients who participated in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ying Y, Yang T, Zhang H, Liu C, Zhao J. Prolonged pituitary down-regulation with full-dose of gonadotropin-releasing hormone agonist in different menstrual cycles: A retrospective cohort study. PeerJ 2019;7:e6837.  Back to cited text no. 1
    
2.
Al-Inany HG, Youssef MA, Ayeleke RO, Brown J, Lam WS, Broekmans FJ. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database of Systematic Reviews. 2016:CD001750. DOI: 10.1002/14651858.CD001750.pub4.  Back to cited text no. 2
    
3.
Haydardedeoǧlu B, Kılıçdaǧ EB. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle. J Turk Ger Gynecol Assoc 2016;17:155-8.  Back to cited text no. 3
    
4.
Siristatidis CS, Gibreel A, Basios G, Maheshwari A, Bhattacharya S. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev. 2015:CD006919. doi:10.1002/14651858.CD006919.pub4.  Back to cited text no. 4
    
5.
Martazanova B, Mishieva N, Korneeva I, Smolnikova V, Abubakirov A. Triggering ovulation with gonadotropin-releasing hormone agonist (GnRHa) and modified luteal support: Hormonal characteristics, embryological and clinical outcome. Fertil Steril 2017;108:e55.  Back to cited text no. 5
    
6.
Taheripanah R, Zamaniyan M, Moridi A, Taheripanah A, Malih N. Comparing the effect of gonadotropin-releasing hormone agonist and human chorionic gonadotropin on final oocytes for ovulation triggering among infertile women undergoing intrauterine insemination: An RCT. Int J Reprod Biomed (Yazd) 2017;15:351-6.  Back to cited text no. 6
    
7.
Cai J, Liu L, Zheng J, Zhang L, Jiang X, Li P, et al. Differential response of AMH to GnRH agonist among individuals: The effect on ovarian stimulation outcomes. J Assist Reprod Genet 2018;35:467-73  Back to cited text no. 7
    
8.
Ou J, Xing W, Li T, Li Y, Xu Y, Zhou C. Short versus long gonadotropin-releasing hormone analogue suppression protocols in advanced age women undergoing IVF/ICSI. Gynecol Endocrinol 2016;32:622-4.  Back to cited text no. 8
    
9.
Kilani Z, Shaban M. A retrospective, observational, single center study of gonadotropin-releasing hormone agonist protocols at the reproductive center of Farah hospital in Jordan. Int J Res Med Sci 2019;7:3103.  Back to cited text no. 9
    
10.
Tsampras N, Fitzgerald CT. Ovarian stimulation protocols. Clinical Reproductive Science. 2018;20:231-40.  Back to cited text no. 10
    
11.
Tsai HD, Chen CM, Lo HY, Chang CC. Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization. Hum Reprod 1995;10:2909-12.  Back to cited text no. 11
    
12.
Albuquerque LE, Tso LO, Saconato H, Albuquerque MC, Macedo CR. Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles. Cochrane Database Syst Rev. 2013:CD002808. doi:10.1002/14651858.CD002808.pub3.  Back to cited text no. 12
    
13.
Maheshwari A, Gibreel A, Siristatidis CS, Bhattacharya S. Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction. Cochrane Database Syst Rev. 2011:CD006919. doi:10.1002/14651858.CD006919.pub3  Back to cited text no. 13
    
14.
Mu ZN, Sun ZG, Song JY, Liu HG, Qiao Y, Xia QC. Effect of duration of gonadotropin releasing hormone agonist on the outcome of in vitro fertilization-embryo transfer in a short-acting long regimen. Libyan J Med. 2019;14:1652058. doi:10.1080/19932820.2019.1652058.  Back to cited text no. 14
    
15.
Varkevisser CM, Pathmanathan I, Brownlee A. Designing and Conducting Health System Research Projects: Proposal Development and Field Work. Vol. 1. Geneva: KIT (pub) Amsterdam, International Development Research Centre (IDRC), Ottawa and WHO; 2003. p. 215-6.  Back to cited text no. 15
    
16.
Cheon KW, Song SJ, Choi BC, Lee SC, Lee HB, Yu SY, et al. Comparison of clinical efficacy between a single administration of long-acting gonadotrophin-releasing hormone agonist (GnRHa) and daily administrations of short-acting GnRHa inin vitrofertilization-embryo transfer cycles. J Korean Med Sci 2008;23:662-6.  Back to cited text no. 16
    
17.
Hsieh Y, Tsai H, Chang C, Lo H. Comparison of a single half-dose, long-acting form of gonadotropin-releasing hormone analog (GnRHa) and a short-acting form of GnRH-a for pituitary suppression in a controlled ovarian hyper stimulation program. Fertil Steril 2000;73:817-20.  Back to cited text no. 17
    
18.
Xie YX, Pan P, Lin HY, Yang DZ, Yu LI. Three GnRH agonist prototols of down regulation on pituitary suppression and pregnancy outcome ofin vitro fertilization in women with normal ovarian reserve: A randomized-control clinical trial. J Sun Yat-sen Univ (Medical Sciences) 2018;39:405-12.  Back to cited text no. 18
    
19.
Tapanainem J, Hovatta O, Juntunen K, Martikainen H, Ratsula K, Tulppala M, et al. Subcutaneous goserelin versus intranasal buserelin for pituitary down-regulation in patient undergoing IVF: A randomized comparative study. Hum Reprod 1993;8:2052-5.  Back to cited text no. 19
    
20.
Duan L, Bao S, Li K, Teng X, Hong L, Zhao X. Comparing the long-acting and short-acting forms of gonadotropin-releasing hormone agonists in the long protocol of IVF/ICSI Cycles: A retrospective study. J Obstet Gynaecol Res 2017;43:1037-42.  Back to cited text no. 20
    
21.
Albuquerque LE, Saconato H, Maciel MC, Tso LO. Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles. Cochrane Database Syst Rev 2005:CD002808.  Back to cited text no. 21
    
22.
Albuquerque LE, Saconato H, Maciel MC, Baracat EC, Freitas V. Depot versus daily administration of GnRH agonist protocols for pituitary desensitization in assisted reproduction cycles: A Cochrane Review. Hum Reprod 2003;18:2008-17.  Back to cited text no. 22
    
23.
Tehraninejad ESh, Nekoo EA, Ezabadi Z, Rashidi BH, Amirchaghmaghi E, Matroud EP. Half-dose, long-acting gonadotropin-releasing hormone agonist (Diphereline) is comparable with daily injections of short-acting gonadotropin-releasing hormone agonist (Suprefact) in IVF/ICSI cycles. Arch Med Sci 2010;6:945-9.  Back to cited text no. 23
    
24.
Geber S, Sales L, Marcos A. Sampaio C. Comparison between a single dose of goserelin (Depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: A clinical endocrinological study of the ovarian response. J Assisted Reprod Genet 2002;19:313-8.  Back to cited text no. 24
    
25.
Wu L, Ren XL, Chen W, Huang B, Zhou YF, Jin L. Influence of different gonadotropin-releasing hormone agonist administration methods on pregnancy outcomes of patients undergoingIn-vitro fertilization-embryo Transfer. Curr Med Sci 2019;39:437-41.  Back to cited text no. 25
    
26.
Mao GH, Feng Z, He Y, Huang YR. Comparisons of the effects of long-acting and short-acting GnRH agonists on embryo quality, endometrial thickness and pregnancy rate in humanin vitrofertilization. Arch Med Sci 2014;10:161-6.  Back to cited text no. 26
    
27.
Liao C, Huang R, Scherer RW, Liang XY. Prognostic factors associated with clinical pregnancy inin vitrofertilization using pituitary down-regulation with depot and daily low-dose luteal phase gonadotropin releasing hormone agonists: A single center's experience. J Hum Reprod Sci 2015;8:30-6.  Back to cited text no. 27
[PUBMED]  [Full text]  
28.
Chen X, Feng SX, Guo PP, He YX, Liu YD, Ye DS,et al. Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization? J Huazhong Univ Sci Technolog Med Sci 2016;36:215-20.  Back to cited text no. 28
    
29.
Chen X, Feng SX, Guo PP, He YX, Liu YD, Ye DS,et al. Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization? J Huazhong Univ Sci Technolog Med Sci 2016;36:215-20.  Back to cited text no. 29
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed411    
    Printed41    
    Emailed0    
    PDF Downloaded106    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]