Friendly IVF: patient opinions

Astrid Højgaard1,3, Hans Jakob Ingerslev1 and Jakob Dinesen2

1 Fertility Clinic and 2 Perinatal Epidemiological Research Unit, Department of Gynaecology and Obstetrics, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: The present trend towards low stimulation protocols in IVF calls for evaluation of patient attitudes. METHODS: This study compared results of a 23-item questionnaire mailed to 167 patients receiving a low stimulation type of regimen (LS-IVF) (unstimulated cycle or clomiphene) and to 116 patients treated by a standard protocol (S-IVF) (long-down regulation with gonadotrophin-releasing hormone analogue and FSH or human menopausal gonadotrophin). RESULTS: Around two-thirds of all responders in both groups deemed side-effects important, but side-effects and stress associated with hormone treatment were more prevalent in patients receiving S-IVF than LS-IVF. Stress due to cycle cancellation was acceptable, mild or not perceptible in significantly (P < 0.005) more patients receiving LS-IVF [48% (36/75)] compared with patients having S-IVF [26% (8/31)]. Of patients having tried the LS-IVF protocol, 93% (125/135) would suggest either LS-IVF or a sequence of this and S-IVF as a future treatment `package' compared with only 53% (33/63) in the S-IVF group ({chi}2 = 43.08, P < 0.0001). The LS-IVF group showed a significant trend towards acceptance of higher number of treatment cycles. CONCLUSIONS: The patients seemed to prefer the simplicity and short duration of a low stimulation regimen in spite of drawbacks such as a high risk of cycle cancellations and accordingly the necessity for more treatment cycles.

Key words: clomiphene citrate/IVF/long down-regulation/unstimulated cycle


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
During recent years attention has been given to hormone stimulation regimens less intensive than the long down-regulation protocol [gonadotrophin-releasing hormone (GnRH) analogue + FSH or human menopausal gonadotrophin (HMG)] in order to reduce side-effects, costs, risks and incidence of multiple pregnancy associated with the latter (Edwards et al., 1996Go; Fleming, 1996Go; Olivennes and Frydman, 1998Go). More cycle cancellations seem unavoidably associated with milder stimulation regimens compared to the long down-regulation protocol, but a comparable cumulative clinical pregnancy rate per embryo transfer was recently achieved in IVF using a clomiphene citrate protocol (H.J.Ingerslev et al., unpublished data). There appear to be no previous studies which have analysed patients' acceptability of low stimulation protocols. Acceptability can be evaluated by measuring patient satisfaction and self-reported levels of stress where patient satisfaction can be defined as the recipient's reaction to the context, process and result of her service experience (Pascoe, 1983Go) and stress as the perceived meaning of an event and self-appraisal of the adequacy of coping resources (Cohen et al., 1995Go). Accordingly, it was the purpose of the present study to evaluate patients' satisfaction and stress associated with each of the two types of protocol in terms of side-effects of hormone treatment, pain at oocyte retrieval, necessity of more treatment cycles, and stress of cancelled cycles in order to point out problem areas and patient preferences in a low stimulation regimen compared with a standard long down-regulation protocol. As unstimulated IVF or low stimulation protocols implies a higher number of cancellations and consequently more treatment cycles (Ingerslev et al., 2001; H.J.Ingerslev et al., unpublished data), this study focused especially on the possible correlation between the number of cycles received and stress reported by the patients.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Two patient groups receiving either a low stimulation type regimen (clomiphene citrate or unstimulated IVF) or a long down-regulation protocol were approached by a questionnaire. In addition to treatment-specific questions they were asked general questions on subjects related to overall satisfaction with the clinic to evaluate if the two patient groups studied were comparable in this aspect.

Low stimulation group (LS-IVF)
Among 564 couples waiting for IVF or intracytoplasmic sperm injection (ICSI) treatment, 196 were invited to participate in a randomized study of IVF in the natural cycle and following clomiphene citrate respectively. Of these, 29 did not respond, 35 were enrolled in a pilot study and finally 132 participated in a randomized study between IVF in unstimulated cycles versus clomiphene citrate stimulation (Ingerslev et al., 2001Go). For the present study, the 167 patients enrolled in the pilot study and the previously published series were selected, hereafter termed the low stimulation group (LS-IVF). All fulfilled the following criteria: age <35 years, infertility unexplained, tubal or due to severe male factor with indication for ICSI, regular menstrual cycles (±3 days), presence of two ovaries and no previous IVF treatment. Patient characteristics and principles for randomization and the two protocols have been presented previously (Ingerslev et al., 2001Go). Following closure of the randomized study, all patients were offered further treatments with clomiphene citrate. During 1997 and 1998, the 167 patients received a total of 452 LS-IVF cycles of which 153 were unstimulated IVF cycles and 299 were stimulated with clomiphene citrate.

In short, at entry to the study, patients were randomized by the sealed envelope method to either clomiphene citrate (Clomivid®; Astra, Albertslund, Denmark) 100 mg from cycle day 3 to day 7 or to IVF in the unstimulated cycle, but with timing of oocyte retrieval by human chorionic gonadotrophin (HCG) injection. All cycles were monitored by vaginal ultrasound. No routine endocrinology was performed, but from day 9 (unstimulated cycle) or 11 (clomiphene citrate) the patients were instructed to test a morning urine sample for LH by a qualitative test (Clearplan®, Unipath Ltd, Bedford, UK). If positive, HCG was given the same morning and oocyte retrieval was performed the following morning. Oocyte retrieval was performed ultrasound-guided transvaginally with a single-lumen needle (Cook®, Brisbane, Australia, 16G) 30 min after the patient had taken 1 g of paracetamol and 10 mg of diazepam orally. No other analgesia was offered routinely. Laboratory culture and ICSI were performed as previously described (Ingerslev et al., 2001Go). A maximum of two embryos were transferred by a Cook®, catheter. No luteal phase support was given. Measurement of serum HCG was performed 2 weeks later and concentrations of >=20 IU/l were considered positive. Pregnant patients were routinely scanned 5 weeks after embryo transfer.

Long down-regulation or standard IVF group (S-IVF)
Among all couples having received their first and subsequent IVF cycles following the long down-regulation protocol (GnRH analogue and FSH or HMG) at our clinic during 1996, 1997 and 1998, 116 couples fulfilled the same criteria as outlined above for the LS-IVF group (H.J.Ingerslev et al., unpublished data). The 116 women had a total of 190 treatments during the period.

Following down-regulation by Suprefact® (Hjechst Marion Roussel, Stockholm, Sweden) nasal spray (six times per day) from cycle day 21 in the previous cycle, ovarian stimulation with FSH or HMG [Humegon®, Puregon® (Organon, Oss, The Netherlands) or Gonal-F®; Serono SA, Madrid, Spain] started 2 weeks later postmenstrually at a standard dose of 150 IU per day. Follicular development was monitored by vaginal ultrasound and HCG (Pregnyl®; Organon) was given 35–36 h before oocyte collection at a follicular diameter of leading follicle(s) of 18 mm. Oocyte retrieval was performed under i.v. sedation with midazolam (1.25–2.5 mg) and pethidine (25–50 mg) and a paracervical block with lidocaine. Oocyte handling, ICSI and embryo culture and transfer was performed as previously described (Ingerslev et al., 2001Go). Luteal support was given i.v. as progesterone (Progestan®; Organon) 100 mg four times daily until the pregnancy test and, if that was positive, until the pregnancy ultrasound 3 weeks later.

Questionnaire
A 23-item questionnaire was designed in a process involving the following steps. The literature was reviewed in order to identify issues of particular importance concerning the patient satisfaction and stress throughout IVF treatments. Three staff members at our fertility clinic (a nurse, an embryologist and a doctor) developed further relevant themes. The questions in the final questionnaire related to the latest treatment cycle (11 questions) and to satisfaction with the amount of information (eight questions) and preferences of treatment (three questions). Finally, respondents were encouraged to comment on the treatment. Scores were measured on a five-point Likert-type scale. Satisfaction concerning information was rated on a scale as follows: very satisfied, satisfied, neutral/do not know, dissatisfied, very dissatisfied. The respondents were asked to characterize the information given as: too optimistic, realistic or too pessimistic. Stress, physical pain and side-effects were rated in the following way: unacceptably severe, severe, acceptable, mild, none. The importance of a question was measured on a three-point scale: very important, important and unimportant. Since the patients in the two groups had no experience as to the alternative treatment protocol, a short neutral description of LS-IVF and S-IVF regimens was offered in the questionnaire (Table IGo).


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Table I. Information in the questionnaire about main characteristics of the low stimulation (LS-IVF) and standard protocol (S-IVF) treatment protocols and results
 
In a pilot study 10 couples were interviewed after having fulfilled the questionnaire. It was confirmed that the topics were considered important and final alterations were made to the questionnaire. Enclosed with the questionnaire was a stamped addressed envelope and a letter in which the aims of the study were described, anonymity was guaranteed and it was emphasized that participation was voluntary. Non-responders were not re-mailed.

Statistical analysis
The results of the questionnaire and background data were entered in a Statistics Package for Social Sciences (SPSS) database and analysed by SPSS software. Bivariate associations were tested with Student's t-test for continuous outcomes, and the {chi}2-test for independence within contingency tables for dichotomous outcome. Statistical significance was defined as two-sided P < 0.05. The risk difference is presented with 95% confidence intervals (CI).


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The response rate was significantly higher in the LS-IVF group (141/167 = 84%) compared with the S-IVF group (66/116 = 57%; {chi}2 = 26.4; odds ratio (OR) 4.1; 95% CI 3.7–4.6; P < 0.0001).

General questions
The two responder groups showed a comparable and high satisfaction (very satisfied or satisfied) with the written information given [LS-IVF 137/141 (97%) versus S-IVF 65/66 (98%)] and verbal information from the doctors [LS-IVF 126/140 (90%) versus S-IVF 58/65 (89%)], nurses [LS-IVF 139/140 (99%) versus S-IVF 64/65 (99%)] and embryologists [LS-IVF 134/140 (96%) versus S-IVF 60/64 (94%)]. Equal proportions of couples in the two groups evaluated the information as satisfactory [LS-IVF 139/141 (99%) versus S-IVF 64/66 (97%)] and the expectations of the two treatments from the information given to be realistic [LS-IVF 131/141 (93%) versus S-IVF 61/65 (94%)]. Accordingly, there was no apparent bias in the self-selection of the responders in terms of general satisfaction to items not directly related to the treatment.

The mean number of started cycles was 1.86 in the LS-IVF group and 1.69 in the S-IVF group. In the last treatment cycle, 72/139 (52%) of the responders in the LS-IVF group had embryos transferred compared with 59/65 (91%) in the S-IVF group. These values are similar to those in the total series [LS-IVF 201/452 (44%) versus S-IVF 164/190 (86%)]. Accordingly, the responder group was representative of all the patients in the two groups in both cases in terms of completed cycles.

In the latest cycle a positive pregnancy test was obtained by 25% (31/123) of LS-IVF responders, significantly higher than the average pregnancy rate of 14% (61/452) in that group ({chi}2 = 9.86; OR 2.2; 95% CI 1.9–2.5). In the S-IVF group these values were 60% (39/65) and 31% (59/190; {chi}2 = 17.15; OR 3.3; 95% CI 2.9–3.8). There was no significant difference between pregnant versus non-pregnant responders in either group in terms of satisfaction with the information given (data not shown).

Specific questions related to the two treatments
Side-effects
Among 75 LS-IVF patients who had been treated with clomiphene, few deemed side-effects unacceptable or severe but more than half of the patients in the S-IVF group did so (Table IIGo). The patients were asked about what importance hormone side-effects had for their general view of the particular treatment. Hormone side-effects were assessed to be important or very important by a comparable proportion of patients in the two groups (Table IIGo). The total stress of the hormone treatment was acceptable, little or not perceptible by 97% (71/73) of the LS-IVF patients compared with 77% (50/65) of the S-IVF patients (Table IIGo). There was no significant difference between pregnant versus non-pregnant responders in either group regarding severity and importance of side-effects (data not shown).


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Table II. Experiences of and attitudes to side-effects of hormone treatment
 
Pain
Among all patients, 12/194 (6%) reported unacceptable pain (Table IIIGo). Although similar proportions of patients in the two groups had experienced a very painful last oocyte retrieval [LS-IVF 45/130 (%) and S-IVF 27/64 (42%)], they had different views on the importance of pain. Significantly more patients in the S-IVF control group regarded pain at oocyte retrieval as an important factor influencing their view of the treatment than in the LS-IVF group (Table IIIGo). The total stress connected with the oocyte aspiration procedure was the same in the two groups, being acceptable, mild or not perceptible in a large majority of the patients [93/131 (71%) versus 44/64 (69%)] (Table IIIGo). The reported pain at oocyte retrieval in both groups was of no difference in pregnant and non-pregnant responders (data not shown).


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Table III. Experiences of, and attitudes to, pain associated with oocyte retrieval
 
Attitudes connected to cycle cancellation and repeated cycles
The stress due to cancellation of a cycle was reported acceptable, mild or not perceptible by a significantly higher proportion of the patients in the LS-IVF group [36/75 (48%)] compared with the S-IVF group [8/31 (26%)] ({chi}2 = 4.50; OR 2.7; 95% CI 1.7–4.1; P < 0.005).

In the LS-IVF group there were no changes in perception of severity of hormone side-effects with increasing number of cycles started. A large majority of patients still found side-effects acceptable even after two or three cycles (data not shown). In the S-IVF treatment group, however, side-effects were more commonly reported as severe if exposed to treatment more than once (one treatment cycle 15/31 versus more than one cycle 22/30; {chi}2 = 3.98; OR 2.9; 95% CI 1.7–5.0; P < 0.005). The opinion on pain seemed to be independent of number of treatment cycles in both groups and the pain reported was independent of number of oocytes aspirated (data not shown). There was no significant difference between pregnant versus non-pregnant responders in terms of attitudes to cycle cancellation (data not shown).

Preference for mode of treatment in the future
Being presented with crude statements about the two protocols (Table IGo), the patients were asked about preferences of either protocol or a combination of the two protocols (for example, two LS-IVF trials followed by two S-IVF trials). Both groups preferred the treatment that they had experienced (Table IVGo). In both groups about half of patients would suggest a combination of the two regimens. However, 93% (125/135) of the patients having tried the LS-IVF protocol would suggest either LS-IVF or a sequence of this and S-IVF compared with only 53% (33/63) in the S-IVF group ({chi}2 = 43.08; OR 11.4; 95% CI 10.2–12.7; P < 0.0001).


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Table IV. Preferences of future treatments according to treatment experienced
 
In the LS-IVF group 74% (23/31) of responders with a positive pregnancy test opted for LS-IVF in comparison with 20% (17/86) of responders with a negative pregnancy test ({chi}2 = 29.74; OR 11.7; 95% CI 9.9–13.7; P < 0.0001). Among S-IVF responders the future choices were not influenced by the results of the treatment (data not shown).

In patients having had LS-IVF, preference for treatment protocol was associated with the perceived pain at the latest oocyte retrieval. Thus, there was a trend to prefer S-IVF alone or a combination of S-IVF and LS-IVF if the last oocyte retrieval had been painful [77% (33/43)] compared with 55% (45/82) if pain was acceptable ({chi}2 = 5.75; OR 2.7; 95% CI 1.9–3.8; P < 0.02). The choices in the S-IVF group were not associated with the severity of pain at the last oocyte retrieval, although this group had indicated pain as an important factor influencing their view of the treatment.

LS-IVF or a combination was preferred by 83% (76/92) of patients who considered hormone side-effects as important, compared with 68% (45/66) who did not ({chi}2 = 4.46; OR 2.2; 95% CI 1.6–3.1; P < 0.05).

When the patients in the two groups were asked to decide how many of either LS-IVF cycles or S-IVF treatments they could accept—in case no pregnancy was achieved—to go through before giving up IVF treatment, there was a significant trend for the LS-IVF group to prefer a high number (>=6) of LS-IVF cycles, whereas the S-IVF group preferred a lower number of LS-IVF cycles (Table VGo). On the other hand, both groups preferred a limited number of S-IVF cycles (<=3).


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Table V. Answers to question on how many of either low stimulation (LS-IVF) cycles and standard protocol (S-IVF) treatments the patients would like to go through before giving up IVF treatment
 
The same trends were evident when the patients were asked to indicate how many of either treatment type they would prefer in a sequential combination of the two (data not shown).


    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The main object of this study was to evaluate how the patients balance advantages and disadvantages of low stimulation regimens in terms of unstimulated cycles or clomiphene for IVF versus a long down-regulation protocol with GnRH analogue and FSH. In broad terms, it was found that the patients seem to counterbalance the disadvantages of low stimulation (less efficiency per cycle, more cancellations) by the apparent advantages (e.g. few side-effects, short duration, simplicity).

Primary domains of satisfaction with fertility treatment are general satisfaction with the clinic, number, duration and results of treatment and information regarding treatment type, side-effects and prognosis (Sabourin et al., 1991Go), all of which were different in the two treatment protocols in the present study. IVF treatment is stressful (Collins et al., 1992Go) and unsuccessful treatment causes grievance and anxiety comparable with that seen following pregnancy loss (Greenfield et al., 1988). The most stressful time points during the procedure are oocyte retrieval, embryo transfer and the 2 week waiting period until the pregnancy test (Connolly et al., 1993Go; Boivin et al., 1998Go), which are all experienced more frequently in an LS-IVF protocol.

In comparison with IVF with GnRH analogue + FSH, low stimulation regimens require more cycles to obtain a comparable pregnancy rate, primarily due to a higher cycle cancellation rate. Accordingly, the patients must undergo a higher number of hormone treatment cycles and oocyte aspiration procedures (Ingerslev et al., 2001; H.J.Ingerslev et al., unpublished data). Low stimulation regimens, on the other hand, are associated with less prominent hormone side-effects, a minimal risk of ovarian hyperstimulation syndrome, a much shorter duration of treatment and a reduction of the risk of multiple pregnancies.

All respondents were generally satisfied with the information given. From other studies it is known that information is a main topic of satisfaction with infertility management (Halman et al., 1993Go; Souter et al., 1998Go).

The higher response rate to the questionnaire in the LS-IVF group compared with the S-IVF group may be explained by a higher motivation for a `new' approach in the former group. This fact and a relative over-representation of patients with positive pregnancy tests among responders in both groups may be borne in mind in the interpretation of the results of this study.

Hormone side-effects were found to be important by a large majority of all responders irrespective of treatment experienced and are thus a main point of interest. A majority of patients in the S-IVF group, but few of the patients receiving clomiphene citrate in the LS-IVF group, reported severe side-effects. With increasing number of cycles the burden of adverse effects in the S-IVF group was more intolerable. No such tendency could be shown in the LS-IVF group where almost no patients reported side-effects.

The information on side-effects in Table IGo given to all couples as a part of the questionnaire represents a possible bias towards the LS-IVF protocol. The reason for presenting Table IGo in the questionnaire was that the patients had experiences with only one of the two treatment protocols. In order to indicate preferences they had to be briefly informed about the main differences between the two protocols in order to make a more informed assessment of the options. The information was rather schematic. The response rate of 96% is interpreted as a sign of high motivation and thus validity.

In the current study, pain at oocyte retrieval was almost identical in the two groups in spite of absence of i.v. analgesia administered in the LS-IVF group. This could not be attributed to the fact that LS-IVF patients had fewer oocytes, as the severity of pain was independent of number of oocytes. While a majority of S-IVF patients regarded pain as important, LS-IVF patients claimed pain to be of less importance. Nevertheless LS-IVF patients showed a marked preference to S-IVF treatment if the last oocyte retrieval had been painful. A possible explanation for this could be that LS-IVF patients, knowing that they were participating in a study, wanted to retreat to a well-known treatment protocol when experiencing a stressful event such as a painful oocyte retrieval. Another possible explanation could be that patients who experience a painful oocyte retrieval may have a wish to optimize outcome of this stage of the treatment procedure. This may reflect the importance of a sufficient analgesia to this group and that painful oocyte retrieval seems to be a predictor of compliance with treatment. On the other hand there was no sign of change in the perception of pain after several unsuccessful treatment cycles. Oocyte retrieval can thus be repeated without increasing the burden of unsuccessful treatments in LS-IVF patients. Previous studies have shown that first and third treatment cycles are the most stressful (Slade et al., 1997Go). After an unsuccessful treatment cycle, 25% of women have a mild or moderate depression (Newton et al., 1990Go). The higher the number of unsuccessful treatment cycles, the more stress (Abbey et al., 1992Go; Connolly et al., 1993Go). However, in a consumer satisfaction study the association between patient satisfaction and number of treatment commencements did not reach significance (Sabourin et al., 1991Go).

The questionnaire was designed to give an answer to the question of whether a less efficient and thus often repeated treatment with a mild stimulation protocol is more or less stressful than a more efficient standard protocol with heavier stimulation and side-effects. A significantly larger proportion of patients found cycle cancellations stressful in the S-IVF group compared to the LS-IVF group. The lesser cancellation stress reported in the LS-IVF group may in part be explained by the fact that there was no limit to the number of treatment cycles in this group, while S-IVF patients were only entitled to three completed cycles. Nevertheless, a majority of S-IVF patients preferred a limit of three S-IVF cycles. Thus, in the LS-IVF group there was a marked tendency to accept more treatments than in the S-IVF group. This indicates that repeated treatments cycles are acceptable within a low stimulation protocol.

The fact is that a rather high proportion of LS-IVF cycles are cancelled, primarily due to spontaneous ovulation (14%) and fertilization failure (21%) (H.J.Ingerslev et al., unpublished data). GnRH antagonists may be useful to obviate risk of spontaneous ovulation in low stimulation protocols.

In conclusion, the present study indicates that a majority of the infertile patients seem to accept the drawbacks of low stimulation regimens in terms of cycle cancellations and accordingly the necessity of more treatment cycles against the advantages of such protocols in terms of few side-effects, simplicity and short duration. These data thus demonstrate that a large proportion of the patients are motivated for low stimulation protocols as an integrated part of available protocols for IVF.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The authors wish to thank clinical, paramedical and laboratory staff at the Fertility Clinic at Skejby Sygehus and at The Perinatal Epidemiological Research Unit, especially Marianne Leth and Bente Jespersen for participation in the development of the questionnaire. We are very grateful to The Danish Institute for Health Technology Assessment for funding (project no. 3126-88-1997).


    Notes
 
3 To whom correspondence should be addressed at: Fertility Clinic, Skejby Sygehus, DK-8200 Aarhus N, Denmark.E-mail: astrid.hoejgaard{at}dadlnet.dk Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Abbey, A., Halman, L.J. and Andrews, F.M. (1992) Psychosocial, treatment and demographic predictors of the stress associated with infertility. Fertil. Steril., 57, 122–128.[ISI][Medline]

Boivin, J., Andersson, L., Skoog-Svanberg, A. et al. (1998) Psychological reactions during in-vitro fertilization: similar response in husbands and wives. Hum. Reprod., 13, 3262–3267.[Abstract]

Cohen, S.J., Kessler, R.C. and Underwood, G.L. (1995) Strategies for measuring stress in studies of psychiatric and physical disorders. In Cohen, S.J., Kessler, R.C., Underwood, G.L. (eds), Measuring Stress: A Guide for Health and Social Scientists. Oxford University Press, New York, pp. 3–25.

Collins, A., Freeman, E.W., Boxer, A.S. and Tureck, R. (1992) Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment. Fertil. Steril., 2, 350–356.

Connolly, K.J., Edelmann, R.J., Bartlett, H. et al. (1993) An evaluation of counselling for couples undergoing treatment for in-vitro fertilization. Hum. Reprod., 8, 1332–1338.[Abstract]

Edwards, R.G., Lobo, R. and Bouchard, P. (1996) Time to revolutionize ovarian stimulation. Hum. Reprod., 11, 917–19.[ISI][Medline]

Fleming, R. (1996) Time to revolutionize ovarian stimulation. Hum. Reprod., 11, 2579.[ISI][Medline]

Greenfeld, D.A., Diamond, M.P. and Decherney, A.H. (1988) Grief reactions following IVF treatment. J. Psychosom. Obstet. Gynecol., 8, 169–174.[ISI]

Halman, J.L., Abbey, A. and Andrews, F.M. (1993) Why are couples satisfied with infertility treatment? Fertil. Steril., 5, 1046–1054.

Ingerslev, H.J., Højgaard, A., Hindkjaer, J. et al. (2001) A randomized study comparing IVF in the unstimulated cycle with IVF following clomiphene citrate. Hum. Reprod., 16, 696–702.[Abstract/Free Full Text]

Newton, C.R., Hearn, M.T. and Yuzpe, A.A. (1990) Psychological assessment and follow-up after in-vitro fertilization: assessing the impact of failure. Fertil. Steril., 5, 879–886.

Olivennes, F. and Frydman, R. (1998) Friendly IVF: the way of the future? Hum. Reprod., 13, 1121–1124.[Free Full Text]

Pascoe, G.C. (1983) Patient satisfaction in primary health care: a literature review and analysis. Eval. Prog. Planning, 6, 185.

Sabourin, S. Wright, J., Duchesne, C. et al. (1991) Are consumers of modern fertility treatments satisfied? Fertil. Steril., 6, 1084–1090.

Slade, P., Emery, J. and Lieberman, B.A. (1997) A prospective, longitudinal study of emotions and relationships in in-vitro fertilization treatment. Hum. Reprod., 12, 183–190.[Abstract]

Souter, V.L. Penney, G., Hopton, J.L. et al. (1998) Patient satisfaction with the management of infertility. Hum. Reprod., 13, 1831–1836.[Abstract]

Submitted on November 1, 2000; accepted on March 19, 2001.