Doi:10.1016/s0301-2115(03)00280-x

European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 Stress relief after infertility treatment—spontaneous conception, aFertility Workgroup—Reproduction Medicine & Endocrinology, Munich University Hospital—City Centre, Ludwig-Maximilian-University, Maistrasse 11, D-80337 Muenchen, Germany bDepartment of Gynecological Endocrinology and Reproductive Medicine, University Medical Center of Obstetrics and Gynecology, Rheinische Friedrich-Wilhelms-University, Sigmund-Freud-Street 25, D-53115 Bonn-Venusberg, Germany cDepartment of Epidemiology & International Health, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd., Ryals Building, Birmingham, AL 35294, USA dDepartment of Gynecological Endocrinology and Reproductive Medicine, University Medical Center of Obstetrics and Gynecology, Christian-Albrechts-University, Brunswiker Street 10, D-24105 Kiel, Germany Objective: In this study, we sought to evaluate characteristics of couples with spontaneous conceptions after treatment with assisted reproductive technologies (ART). Study design: Data from 254 couples who underwent 1127 therapy cycles between November 1987 andFebruary 1997, were analyzed. Chi-Square (w2) test and Student’s t-test were used. P < 0:05 was considered significant. Results: Spontaneouspregnancies occurred in 14% of all treated couples. Psychological counselling only was performed in 21% but was observed significantly morefrequently among patients without later spontaneous conception. Ten percent of all treated couples applied for adoption. The miscarriage ratewas significantly higher in the group of treatment dependent pregnancies compared to the group of patients with later spontaneous conception(27% versus 9%). The spontaneous conception rate differed significantly depending on women’s age and normal semen analysis. Conclusion:Appearance of spontaneous conception after ART-procedures should be taken into account in the first patient’s interview. Depending onwomen’s age and andrological parameters, treatment-success will differ. The positive impact of psychological counselling for stress reliefduring and after therapy should also be noted, even though a statistically significant impact could not be demonstrated in the present study.
Adoption should be discussed as an alternative to overcome infertility.
# 2003 Elsevier Ireland Ltd. All rights reserved.
Keywords: Spontaneous conception; Infertility treatment; Adoption; Psychological counseling; Miscarriage investigations have focused on the impact of psychologicalcounseling on the success-rate of ART-procedures without It is well established that spontaneous pregnancies after regarding the period afterwards. Only a few studies have infertility therapy occur even in cases with severe subfertility focused on the employment of psychological counseling after . Most studies focus on treatment-independent pregna- ncies after in vitro fertilization (IVF) . Little is known Before intracytoplasmic sperm injection (ICSI) became a about the instance of spontaneous conception in couples standard ART-procedure and gestational surrogacy arrange- where different assisted reproductive technology (ART) pro- ments were legalized in some countries, adoption and donor insemination were common alternatives for couples with Several studies have evaluated interference of psychologi- severe male subfertility In some cases, adoption still cal adjustment of infertile couples Anxiety, depression, represents an option for couples after unsuccessful ART self-esteem, and marital satisfaction were analyzed using treatment Researchers have explored the correlation different scales and checklists. However, most of these of stress relief, spontaneous conception, and adoption sepa-rately to ART treatment However, little information is available concerning the interaction of all three aspects Corresponding author. Tel.: þ49-89-5160-4678; and their correlation to ART treatment. On the other hand fax: þ49-89-5160-4918.
E-mail address: mail@kupka.info (M.S. Kupka).
women’s age, semen analysis parameters, and duration of 0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/S0301-2115(03)00280-X M.S. Kupka et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 infertility are well known prognostic factors in ART-proce- intra-fallopian transfer was performed. On average, each dures and are therefore also analyzed in the present couple underwent 4.5 treatment-cycles (range 1–12, S.D. 3.8).
A clinical pregnancy was defined as the occurrence of at least one ultrasonography-confirmed gestational sac (whichexcludes biochemical pregnancies) with confirmation of positive heartbeats. For IVF and ICSI procedures, the cal-culation of the clinical pregnancy rate was related to the Between November 1987 and February 1997, a total of embryo transfer; for GIFT procedures it was related to 1127 therapy cycles were performed in 254 couples at an gamete transfer. A live birth was described as a treatment University Medical Center in Germany. These cycles cycle that resulted in at least one live born neonate with included controlled ovarian hyperstimulation (COH), intrau- a minimum gestational age of 25 weeks. Analysis was terine homologues insemination (IUI) with and without restricted to only one spontaneous conception per couple.
ovarian stimulation, IVF with and without ICSI and, in rare Two study groups were established: those without sponta- cases, gamete intra-fallopian transfer (GIFT). In accordance neous conception after infertility treatment (Group I) and with the German Embryo Protection Act and the guide- those with spontaneous conception after infertility treatment lines of the German Medical Association, no donor program (Group II). Semen analysis parameters were used as recom- in IVF/ICSI procedures was established, a maximum of Concentration >20 Â 106/ml, motility >40%, normal morphology >40% Concentration <20 Â 106/ml, motility >40%, normal morphology >40% Concentration >20 Â 106/ml, motility <40%, normal morphology >40% Concentration >20 Â 106/ml, motility >40%, normal morphology <40% Concentration <20 Â 106/ml, motility <40%, normal morphology <40% three embryos could be transferred, and fertilized oocytes Chi-Square (w2) analysis, Student’s t-test, and confidence were frozen in the pronuclear stage.
intervals were calculated. P < 0:05 was considered signifi- In this study, cycles with frozen–thawed embryo transfer, cant. Data entry and analysis were performed using SPSS azoospermia, and bilateral tubal occlusion were excluded.
Two women who changed their partners during the observa-tion period were also excluded.
During the time span nearly 4900 couples were treated at the department. The analyzed treatment cycles were con-ducted by only one physician from the University Medical 3.1. Characteristics of the study population Center in order to reduce bias attributable to differenttreatment-strategies and clinical experiences.
Women’s age ranged from 23 to 43 years with a mean of Calculation of women’s age was fixed at the beginning of 33.7 years (A statistically significant difference the ART treatment. The follow-up interval lasted 9–60 was observed for both groups (P ¼ 0:049). Women without months and ended in September 1997. After ART-proce- a spontaneous conception were older than Group II women dures were performed, all couples decided not to continue (33.9 versus 32.2 years). The highest rate of spontaneous conceptions (44%) occurred in women aged 31–35 years.
The medical records for all 254 couples were analyzed for Men ranged in age from 19 to 62 years, with a mean of 36.1 history of infertility as well as for information following years. No statistically significant difference was observed the treatment. In addition, 142 couples completed a detailed questionnaire evaluating resort to psychological counsel- A mean duration of infertility of 3.7 years was observed ing and application of adoption. The questionnaire was among all 226 couples and varied from 3.1 (Group II) to 4.0 pre-tested by employees of the department. Eighty-four years (Group I), although this difference was not statistically telephone interviews were conducted using a standardized format, yielding information for a final group of 226 couples Almost three out of four (74%) couples in Group I were undergoing a total of 1005 treatment cycles.
found to have primary infertility at the beginning of ART- Most of the 1005 treatment cycles were performed as procedures. The rate was higher for Group II couples (88%) IUI (368) or controlled ovarian hyperstimulation (237).
although the difference was not statistically significant.
The more invasive treatments were represented by 208 Tubal disease was identified as the main infertility diagnosis IVF-cycles and 166 ICSI-cycles. In 26 cases a gamete for 8% of Group I and for 9% of Group II couples. Severely M.S. Kupka et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 Table 1Characteristics of the study population a Couples without later spontaneous conception.
b Couples with later spontaneous conception.
c Oligoasthenoteratozoospermia.
reduced sperm quality as the sole infertility factor was The outcome of 71 treatment dependent pregnancies described in 31% of Group I couples, compared to 19% showed a miscarriage rate of 27% and a live birth rate of of Group II couples. No statistically significant differences 73% (This was a statistically significant difference were found with regard to infertility diagnoses.
from the clinical outcome of Group II pregnancies. A lowermiscarriage rate (9%) was associated with a higher live birth rate (91%). No ectopic pregnancy or induced abortion wasreported.
Thirty-two out of 226 couples reported a spontaneous Group II couples underwent less invasive treatments such conception after ART treatment, indicating a spontaneous as intrauterine insemination or ovarian stimulation more often. IVF was performed in 14% of Group II and 22% Fifteen treatment-related conceptions occurred in this of Group I patients. ICSI was performed in only 9% of group (). Nevertheless, successful ART treatment Group II patients and in 18% of Group I patients. The showed no statistically significant difference in the two treatment dependent clinical pregnancy rates demonstrated no statistically significant differences between the twogroups Clomiphene citrate (CC) or human menopausal gonado- tropin (HMG) were typically used for controlled ovarian Clinical pregnancy rate in ART procedures hyperstimulation procedures (426 and 492 of 908 cycles, a Treatment cycles.
b Couples without later spontaneous conception.
a The percentages refer to the total number of each column.
c Couples with later spontaneous conception.
b All pregnancies were twin pregnancies.
M.S. Kupka et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 16
15
14
13
12
11
10
% spontaneous pregnancy rate
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56
months after ART-procedures
Fig. 1. Cumulative spontaneous pregnancy rate: (a) in all 32 spontaneous conceptions; (b) in couples with former treatment dependent pregnancies (N ¼ 15);(c) in couples with no former treatment dependent pregnancy (N ¼ 17).
respectively). Gonadotropin releasing hormone-antagonists of women with treatment dependent pregnancies underwent (GnRh-A) and, in most instances also agonists, were not psychological counseling. This was not statistically different available during that period. No statistically significant difference was observed in the comparison between thedrug therapies for Groups I and II cycles.
The time between the end of ART-procedures and spon- taneous conception ranged from 6–56 months, with an Comparing results from the first semen analysis per- average period of 19 months ). Eighty-four percent formed at the department, normozoospermia was found in of the couples with spontaneous conception became preg- 39% of Group I and in 59% of Group II couples, a statis- tically significant difference (P ¼ 0:03) (). In couples During the first 18 months, 80% of the couples with a with treatment dependent pregnancies, normozoospermia former successful ART treatment conceived spontaneously, was found in 47%. This was not statistically different to compared to only 47% of those without a former successful the group of patients with treatment dependent pregnancies.
ART treatment. Although the results showed no statistically There were no statistically significant differences observed significant difference, a former successful ART treatment for other classifications such as oligozoospermia, astheno- zoospermia, teratozoospermia, or OAT-syndrome.
Comparing the group of patients with treatment depen- 3.3. Adoption and psychological counseling dent pregnancies and later spontaneous conceptions, nosignificance was detected with regard to the distribution Overall, only 22 of all 226 couples (10%) applied for of normal semen analysis. Among patients with treatment adoption (), consisting of 17 couples without later dependent pregnancies, 47% of the tests showed normal spontaneous conception and 5 Group II couples. During results. An OAT-syndrome was found in 10% of Group I and ART treatment, four of the five couples with later sponta- neous conception applied for adoption, compared to 6 out of17 couples in the group without spontaneous conception.
None of these differences were found to be statistically Over one in five couples (21%) agreed to psychological Improvements in all aspects of assisted reproductive counseling (This included only two Group II technologies have increased pregnancy rates among sub- couples (6%) and 45 couples (23%) from Group I, a dif- fecund couples. For example, in Japan and in France, ference that was statistically significant (P ¼ 0:03). Both spontaneous conception after delivery of an IVF-baby Group II couples underwent psychological therapy during was observed in 18 and 9% of couples, respectively ART treatment. In Group I, 30 couples (67%) decided to Without considering treatment dependent success undergo psychological therapy during ART treatment and 15 in an IVF group, a spontaneous conception rate of 7% was couples underwent this therapy afterwards. Sixteen percent reported separately by Roh et al. and Haney et al. .
M.S. Kupka et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 Excluding only bilateral tubal occlusion, spontaneous preg- nancy rate of 11% was observed versus 7% in the group nancies were found among 8% of Israeli couples of patients without later spontaneous conception. Primary Excluding additional azoospermia in an IVF group, a spon- and secondary infertility were analyzed at the beginning of taneous pregnancy rate of 11% was determined by Vardon ART-procedures. At this time a previous pregnancy seemed et al. Without consideration of the preceding ART not to have any influence on the later spontaneous concep- treatment, Merzoug et al. found 16% treatment inde- tion. Secondary infertility with at least one former conception pendent pregnancies. Hennelly et al. found subsequent was seen more often in the group without later spontaneous spontaneous conception in 21% of couples who underwent conception and appeared to have no influence, as has also In the present study, spontaneous pregnancies occurred in Most of the spontaneous conceptions were observed 14% of all treated couples. This also could be related to within a period of 2 years after the termination of ART- patients’ work up to avoid unnecessary ART treatments. The procedures This period was similar to 18 months quality of diagnostic procedures and characteristics of cou- ples therefore should be evaluated. Women now are older An increased rate of miscarriages in women undergoing when asking for IVF-treatment. The annual report 1996 of ART-procedures was described in sundry investigations the German IVF Registry demonstrate that IVF-treatment . In the United States, at least 15% of spontaneous was performed in 29.7% in women aging 35–40 years and in abortions were found in women undergoing ART-proce- 9.0% in women aging more than 40 years. In 2001, this dures . The overall miscarriage rate in the present study changed to 32.7 and 10.6%. Health insurances in Germany was 21%, and showed a statistically significant difference in now are objecting a detailed checklist before paying for an the two groups. It should be noted that the number of patients IVF-treatment (for example two sperm-counts in a period of was relatively small and the significance was seen as having 3 months with fixed limits for morphological criterias are no great statistical power (P ¼ 0:046).
necessary for ICSI-treatment). So the diagnostic pathway Undergoing an ART-procedure is not usually indicative of signs or symptoms of psychological maladjustment .
In the present study, 71 of 226 couples conceived as a Nevertheless, for men and women ART-procedures can be result of successful ART treatment. Five factors help to stressful . Stress management groups and short courses explain the relatively low treatment dependent success rates.
of psychotherapy during ART-therapy have been described First, treatments were performed in a period where new by Brandt and Zech and by McNaughton-Cassill et al.
techniques and substances for controlled ovarian hypersti- . Poehl et al. described that 18% of a sizeable mulation were being introduced and established. Second, a collective underwent psychotherapeutic counseling and relatively high rate of male infertility (30%) also influenced another 10% would commit to undergoing treatment. In success rates. Third, ovarian stimulation was employed in the present study, 21% of the couples decided to undergo only a moderate extent, so that no higher multiple pregnan- psychological treatment with a statistically significant dif- cies occurred. Fourth, legislation in Germany limits the number of transferred embryos to a maximum of three Among patients without spontaneous pregnancies, the and prohibits embryo selection and donor-programs.
frequency was significantly higher. A positive correlation Fifth, a tertiary-care hospital restricted patient selection between psychological counseling and the occurrence of to a certain group, the majority of whom had been unsuc- spontaneous pregnancies after ART-procedures could cessfully treated in other reproductive units. Furthermore, not therefore be demonstrated in this study. The results there must be a negative bias of patient’s selection in the could indicate a correlation to longer ongoing infertility department because the pregnancy rate per transfer in all and therefore a more stressful non-adjustment to ART 7200 IVF/ICSI cycles ranged from 12.0 to 27.2% between therapies. Psychological counseling presented a diversity of therapy techniques so that a detailed evaluation was not The likelihood of spontaneous conception after ART- therapy is significantly higher in some groups of patients.
Seventy percent of the couples started the treatment One of the most important prognostic factors for infertility while undergoing ART-procedures. Although IVF-units in treatment is woman’s age This was also seen with Germany were not committed, at that time, to offering spontaneous conception in our study, where a statistically psychological counseling, this altered, so that it became significant difference was determined between patients with easier for couples to gain this support at the same clinic.
and without later spontaneous conception. The duration Stress relief could be observed not only through acceptance of infertility undoubtedly is related to age but showed no of childlessness, but also by alterations in personal situations . In six couples, spontaneous conception became appar- A correlation between successful ART-therapy and the probability of spontaneous conception was determined, as In general, differences in psychological characteristics has also been shown by Fadini et al. Among those with between couples with and without fertility disorders could later spontaneous conception, a treatment dependent preg- not be seen in a study of 564 German couples M.S. Kupka et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 190–195 Due to the rigorous requirements and extensive delays in [10] Renne D. There’s always adoption: the infertility problem. Child the adoption process, most German couples adopt a young [11] Moody R. Adoption—women must be helped to consider all their child from abroad. German couples probably apply more options. BMJ 2001;323(Oct (7317)):867.
frequently for adoption due to the restrictions imposed by [12] Harrison RF. In: Edinburgh Churchil BJ, editor. Stress in infertility.
the German Embryo Protection Act, which does not permit Recent advances in obstetrics and gynaecology. Livingstone; 1990.
any kind of donor-program to be offered in an IVF-treatment [13] Dicker D, Goldman JA, Ashkenazi J, Feldberg D, Shelef M, Levy T.
Age and pregnancy rates in in vitro fertilization. J In Vitro Fert In our study, 10% of the couples applied for adoption— Embryo Transf 1991;8(Jun (3)):141–4.
nearly half of them in the course of an ART-procedure.
[14] Leiblum SR, Kemmann E, Colburn D, Pasquale S, DeLisi AM.
Renne entitled his study ‘‘There is always adoption’’ Unsuccessful in vitro fertilization: a follow-up study. J In Vitro Fert This seemed to be the motivation for application, even when Embryo Transf 1987;4(Feb (1)):46–50.
bureaucratic barriers had to be accepted.
[15] Gesetz zum Schutz von Embryonen (Embryonenschutzgesetz— Appearance of spontaneous conception after ART-proce- dures should be taken into account in the first patient [16] World Health Organization, Laboratory manual for the examination interview. Depending on the age of the woman and the andro- of human semen and semen-cervical mucus interaction, 3rd ed. New logical parameters, treatment-successes will differ. Positive York: Cambridge University Press; 1993.
impact of psychological counseling for stress relief during [17] Shimizu Y, Kodama H, Fukuda J, Murata M, Kumagai J, Tanaka T. Spontaneous conception after the birth of infants conceived and after the procedure also should be noted, even when a through in vitro fertilization treatment. Fertil Steril 1999;71(Jan (1)): statistically significant impact could not be demonstrated in the present study. Adoption as one alternative to overcome [18] Olivennes F, Kerbrat V, Rufat P, Blanchet V, Fanchin R, Frydman R.
infertility should be discussed, assisted by a qualified self-help Follow-up of a cohort of 422 children aged 6 to 13 years conceived group or social work agency representative.
by in vitro fertilization. Fertil Steril 1997;67(Feb (2)):284–9.
[19] Roh SI, Awadalla SG, Friedman CI, Park JM, Chin NO, Dodds WG, et al. In vitro fertilization and embryo transfer: treatment-dependentversus independent pregnancies. Fertil Steril 1987;48(Dec (6)):982–6.
[20] Haney AF, Hughes CL, Whitesides DB, Dodson WC. Treatment- independent, treatment-associated, and pregnancies after additional [1] Hennelly B, Harrison RF, Kelly J, Jacob S, Barrett T. Spontaneous therapy in a program of in vitro fertilization and embryo transfer.
conception after a successful attempt at in vitro fertilization/ Fertil Steril 1987;47(Apr (4)):634–8.
intracytoplasmatic sperm injection. Fertil Steril 2000 Apr;73(4)774–8.
[21] Fadini R, Mignini-Renzini M, Boneschi A, Rinaldi M, Catanzaro F, [2] Merzoug K, Gerhard I, Runnebaum B. Incidence and prerequisites Della Morte E. Spontaneous pregnancy in ‘‘sterile couples’’. Arch for therapy-independent pregnancy in sterile patients. Geburtshilfe Ital Urol Androl 1993;65(Apr (2)):197–9.
Frauenheilkd 1990;50(March (3)):177–88.
[22] Levy T, Ashkenazi J, Feldberg D, Shelef M, Goldman JA. The [3] Ben-Rafael Z, Mashiach S, Dor J, Rudak E, Goldman B. Treatment- prognostic value and significance of preclinical abortions in in vitro independent pregnancy after in vitro fertilization and embryo transfer fertilization-embryo transfer programs. Fertil Steril 1991;56(Jul trial. Fertil Steril 1986;45(Apr (4)):564–7.
[4] Vardon D, Burban C, Collomb J, Stolla V, Erny R. Spontaneous [23] Tatham LM, Schieve L, Jeng G. Spontaneous abortion and assisted pregnancies in couples after failed or successful in vitro fertilization.
reproductive technology in the United States. Paediatr Perinat J Gynecol Obstet Biol Reprod (Paris) 1995;24(8):811–5.
[5] Bringhenti F, Martinelli F, Ardenti R, La Sala GB. Psychological [24] Greenfeld DA. Does psychological support and counseling reduce adjustment of infertile women entering IVF treatment: differentiating the stress experienced by couples involved in assisted reproductive aspects and influencing factors. Acta Obstet Gynecol Scand technology? J Assist Reprod Genet 1997;14(Apr (4)):186–8.
[25] McNaughton-Cassill ME, Bostwick JM, Vanscoy SE, Arthur NJ, [6] Brandt K, Zech H. Results of a prognosis study of in vitro Hickman TN, Robinson RD, et al. Development of brief stress fertilization after brief psychotherapy. Geburtshilfe Frauenheilkd management support groups for couples undergoing in vitro fertilization treatment. Fertil Steril 2000;74(Jul (1)):87–93.
[7] Kainz K. The role of the psychologist in the evaluation and treatment [26] Poehl M, Bichler K, Wicke V, Dorner V, Feichtinger W.
of infertility. Womens Health Issues 2001;11(Nov–Dec (6)):481–5.
Psychotherapeutic counseling and pregnancy rates in in vitro [8] Owens DJ, Edelmann RE, Humphrey ME. Male infertility and donor fertilization. J Assist Reprod Genet 1999;16(Jul (6)):302–5.
insemination: couples’ decisions. Hum Reprod 1993;8(Jun (6)):880–5.
[27] Wischmann T, Stammer H, Scherg H, Gerhard I, Verres R. Psycho- [9] Holbrook SM. Adoption, infertility, and the new reproductive social characteristics of infertile couples: a study by the ‘Heidelberg technologies: problems and prospects for social work and welfare Fertility Consultation Service’. Hum Reprod 2001;16(Aug (8)): policy. Soc Work 1990;35(Jul (4)):333–7.

Source: http://prof-kupka.de/stress_relief.pdf