Adjusting to life when assisted conception fails.

According to our basic (psychosomatic) tenet, every somatic problem has its emotional side; therefore, medical treatment and counselling are not separate but are interlinked and equally important. First interviews and interviews after failed assisted reproductive technology (ART) are held together in four person settings; the couple with two counsellors. The sessions last for approximately 1 h. The aim is to help patients escape the agonizing and distressing state in which they are kept by their foci (psychogenic aspects causing distress). Stress and iatrogenic factors are discussed and when patients are able to re-experience their suffering, many possible psychological effects on infertility and/or treatment failure are explored. If the patients consciously perceive these mechanisms of action, they will turn to their basic emotional needs and perspectives; approximately 30% of them will conceive later while approximately 20% opt for adoption. However, half of the patients take no positive action, neither giving up nor continuing with activities for a child. Nor do they seek counselling. The analysis of many of their reports argues in favour of an adaptive model for coping with reproductive failure.

Prognostic appraisal of success and failure in an in vitro fertilization program by transvaginal Doppler ultrasound at the time of ovulation induction.

In 323 stimulated cycles of women participating in in vitro fertilization treatment, a transvaginal Doppler examination was performed on the day of ovulation induction to investigate the value of blood flow velocimetry of the uterine artery. The results showed a significantly lower pulsatility index in patients who conceived (n = 42) compared with those who did not become pregnant (n = 272). The differences were especially marked during the first cycles. These results suggest that studies of the uterine hemodynamic response are useful in appraising the likelihood of success of implantation after embryo transfer.

[Ultrasound monitoring of follicle growth in IVF]. / Ultraschallmonitoring des Follikelwachstums bei der IVF.

Vaginal sonography is a well-established method to monitor follicular growth and to detect the optimum time for induction of ovulation with hCG. In this study we found significantly less and smaller follicles in the left ovary compared to the right. However, during the procedure of oocyte retrieval we found an equal number of follicles and oocytes in both ovaries. We assume therefore that the used sonographic method is less valid for the left ovary compared to the right. The reason could be that on the left side the ovary is often hidden behind the sigma which makes visualization by ultrasound more difficult. Vaginal sonography should therefore be performed on a gynecological chair where it is easier to bring the probe closer to the left ovary. On the basis of follicular fluid volume measurements at the puncture the sizes of the follicles on day hCG were calculated and resulted in a range of 14.7-20.7 mm for the average of all follicles.

[Vaginal ultrasonographic observation of uterine contractions in embryo transfer and its relevance to treatment success]. / Die vaginosonographische Beobachtung von Uteruskontraktionen beim Embryotransfer und ihre Relevanz im Hinblick auf den Behandlungserfolg.

441 patients were treated by in-vitro fertilisation and embryo transfer (ET) from January 1989 to May 1990. Transvaginal ultrasound allowed pre-transfer assessment of the uterine architecture and confirmation of successful transfer after the procedure. The length and direction of the cervical and uterine cavity were noted. The real-time image was observed for one minute to see, if uterine contractions occurred. These can be clearly seen as pulsatile movements, which can be distinguished from breathing motions. We also recognised the localisation and the movement of the transferred air bubble. A "double bubble sign" occurs as a result of the two air bubbles being seen in sagittal transvaginal ultrasound. The embryos are sandwiched between the two visible bubbles. As far as the subjective methods used permit a definitive statement, there is no connection between contractions, localisation and movement of the air bubble with the success or failure of the E.T.

[Comparison of various methods of cryopreservation of human pre-embryos]. / Vergleich verschiedener Methoden der Kryokonservierung humaner Prä-Embryonen.

A human egg and embryo freezing program for non-fertilized eggs and spare embryos has been established in our in vitro fertilization clinic. In the following we report on our first experience with different methods of human pre-embryo cryopreservation. In a simple evaluation we have compared different conventional freezing techniques using cryoprotectant substances such as glycerol, DMSO and 1.2 propanediol and an "ultrarapid" technique. So far we have achieved 6 normal ongoing and 2 biochemical pregnancies out of a total number of 61 embryo transfers. This equals 9.8% pregnancy rate per embryo transfer. Two methods seem preferable, i.e. sucrose and 1.2 propandiol which has the highest success rate and the ultrarapid method which gives a good rate of embryo survival on the one hand and a simple handling on the other.

Experience with a new fixed-stimulation protocol without hormone determinations for programmed oocyte retrieval for in-vitro fertilization.

A new fixed schedule of ovarian stimulation for in-vitro fertilization (IVF) was developed that is not only simpler and easier to handle for the patients but also gives a better fertilization and pregnancy rate. The period and the start of stimulation is shifted by means of a contraceptive pill in such a way that stimulation is generally started on a Sunday. The patient takes clomiphene, (100 mg) for 5 days and prednisolone (7.5 mg) for 30 days to suppress possible exaggerated adrenal androgens, and receives 150 IU human menopausal gonadotrophin (HMG) i.m. every other day from her doctor at home. From the 8th day of stimulation onwards follicular growth is registered by daily ultrasound at the IVF centre. A dose of 5000 IU human chorionic gonadotrophin (HCG) is given when the dominant follicle exceeds 18 mm diameter. Blood sampling for hormone estimations is not necessary and only one sample of urine is needed for the luteinizing hormone (LH) estimation before HCG. In comparison to clomiphene only, clomiphene plus HMG/follicle stimulating hormone (FSH) and HMG/FSH only, this protocol resulted in a significantly higher fertilization and pregnancy rate per follicular puncture. The rate of abortions and extrauterine pregnancies, on the other hand, was decreased. When comparing repetitive IVF cycles with the first IVF cycle, a significant reduction of oocytes in repetitions was found, while there was no difference found in the number of fertilized eggs. The pregnancy rate, on the other hand, was increased in the repeat-cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

A fixed stimulation protocol for in vitro fertilization (IVF) without determinations of hormones in blood.

A new fixed schedule of ovarian stimulation for IVF was developed, which is not only simpler and easier to handle for the patients but also yields better fertilization and pregnancy rates. The period and beginning of stimulation are shifted by means of a contraceptive pill, so that stimulation can generally be started on a Sunday. The patient takes 100 mg clomiphene for 5 days and 7.5 mg prednisolone for 30 days to suppress possible exaggerated adrenal androgens; she also receives 150 IU of human menopausal gonadotropin (HMG) i.m. every other day from her family physician. From the 8th day of stimulation onwards, follicular growth is registered by daily ultrasound at the IVF center. When the dominant follicle exceeds 18 mm in diameter, 5000 IU human chorionic gonadotrophin (hCG) is given. Blood sampling for hormone estimations is not necessary, and only one sample of urine is needed for the LH estimation before hCG. In comparison to clomiphene citrate (Clomid) alone, Clomid plus HMG/FSH and HMG/FSH alone, this protocol resulted in significantly higher fertilization and pregnancy rates per follicular puncture. The rate of abortions and extrauterine pregnancies, on the other hand decreased. When comparing repetitive IVF cycles with the first IVF cycle, a significant reduction of oocytes in repetitions was found, but no difference was found in the number of fertilized eggs. The pregnancy rate, on the other hand, increased in the repeat cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of unruptured ectopic pregnancy by needling of sac and injection of methotrexate or PG E2 under transvaginal sonography control. Report of 10 cases.

We report transvaginal puncture of ectopic pregnancy and instillation therapy under sonographic control in 10 cases. Only patients with rising beta-hCG levels were selected for treatment. In 9 cases we instilled methotrexate and in 1 case prostaglandin E2. A successful outcome was obtained in 8 patients, 7 had been treated with methotrexate and 1 with PG E2. Conservative treatment failed in two patients. However, these patients were already in the 10th and 8th week of pregnancy, respectively. There were no side effects after methotrexate; the patient given PG E2 experienced severe discomfort, vomiting and cramps.

PIP: The authors report transvaginal puncture of ectopic pregnancy and instillation therapy under sonographic control in 10 cases. Only patients with an increase in beta-hCG levels were selected for treatment. In 9 cases, the authors instilled methotrexate and in 1 case, prostaglandin E2 (PGE2). A successful outcome was obtained in 8 cases, 7 having been treated with methotrexate and 1 treated with PGE2. conservative treatment failed in 2 patients. However, these patients were already in the 8th week of pregnancy. There were no side effects after methotrexate; the patient who received PGE2 experienced severe discomfort, vomiting, and cramps.

Studies on psychosomatic implications of infertility--effects of emotional stress on fertilization and implantation in in-vitro fertilization.

A case report shows the long and stony path of a couple who had to go through eight attempts at IVF in 4 years until the desired child was achieved. The psychosomatic implications of the various 'failures' of treatment become clearer when compared with the results of a psycho-endocrinological questionnaire completed by 551 patients and 115 controls since 1982. This questionnaire contains among others the Giessen personality test for the image of self, mother and father, a somatic complaints score to evaluate the severity of autonomic disorders, items for the presence and severity of possible gynaeco-endocrinological symptoms and items to evaluate the reference persons and their changes during childhood. The following results could be obtained. In a comparison of the means of 58 different somatic complaints, patients rated significantly higher than controls (P = 0.002). Women with menstrual disturbances, menstrual pains, acne or unclear skin or dry skin also suffered more from other complaints. These symptoms were also correlated with a higher score for depressive mood. Those women who were not brought up by both parents during their childhood also scored significantly higher (P less than 0.0001) in the somatic complaints score. In the Giessen personality test patients appeared significantly more compulsive (P less than 0.002) and depressive (P = 0.003) than the controls and identified themselves more with their mothers. From 60 patients in our IVF programme, 19 had no fertilization of oocytes and scored significantly higher (P = 0.008) on the social potency scale than did the patients with fertilized oocytes. Women with unsuccessful treatments in terms of pregnancy scored significantly higher in the social resonance and social potency tests. We interpret this exaggerated positive attitude as an attempt to overcome inner fears, doubts and ambivalences. These results support the importance of psychosomatic aspects in infertility and reassure us of the necessity of including counselling in any infertility treatment, including IVF.

[Transvaginal Doppler sonography for measuring blood flow in the pelvis]. / Transvaginale Doppler-Sonographie zur Blutflussmessung im kleinen Becken.

This is a report on our first experience with transvaginal Doppler sonography. In this way we can measure the different blood flow parameters in the internal iliac, ovarian and uterine arteries during the menstrual cycle. The detection of the particular vessels and their typical waves of flow are described in detail. In 279 measurements taken from 107 patients in the stimulated cycle we could show that the systolic blood flow after induction of ovulation or before ovulation increases significantly both in the internal iliac and in the ovarian artery. This experience made in the stimulated cycle could also be confirmed in the natural cycle where a preovulatory increase of systolic blood flow in the uterine artery was also noticed. During administration of a contraceptive pill only slight uncoordinated increases of blood flow could be registered. Any possible connections between the above mentioned changes with factors depending on the blood flow or on organic resistance on one hand or on endocrine parameters on the other, and possible practical applications, are discussed.

Prednisolone supplementation to Clomid and/or gonadotrophin stimulation for in-vitro fertilization--a prospective randomized trial.

In a prospective randomized trial, 73 patients received prednisolone, 7.5 mg daily, for one cycle in addition to Clomid and/or gonadotrophins, while another 73 patients were not given the corticosteroid. In-vitro fertilization (IVF) resulted in 16 versus six clinical pregnancies in the prednisolone and the non-prednisolone group, respectively (P less than 0.05). Oestrogen was significantly higher under prednisolone during the ovulatory phase, while LH was significantly lower. The adrenal androgen dehydroepiandrosterone sulphate was markedly depressed by prednisolone and testosterone was also markedly lower in the prednisolone group. A stress-related androgen excess might occur in some patients undergoing IVF with consequent cystic degeneration of some follicles as in polycystic ovarian disease. Prednisolone might counteract this detrimental effect by depressing adrenal and ovarian androgens.

Smoking and in-vitro fertilization.

One-hundred and fourteen patients who underwent IVF treatment were asked about their smoking habits. Their rhodanide (SCN) concentrations were then estimated in serum and follicular fluid. SCN has been identified as an indicator for the amount of cigarettes smoked. The IVF outcome of non-smokers was compared with that of the smokers and no significant differences of fertilization rate and pregnancy rate between the two groups were found, but the SCN concentrations in serum and follicular fluid were increased in smokers (P less than 0.05). The effect of cigarette smoke toxins was perhaps not observable because other factors influencing the IVF treatment could possibly overlap with the influence of these particular toxins.

Transvaginal sector scan sonography for needle guided transvaginal follicle aspiration and other applications in gynecologic routine and research.

A transvaginal sector scanner probe has been developed for precise needle-guided transvaginal follicle aspiration under sonographic control. The first results of transvaginal needle-guided follicle aspiration are presented. A high recovery rate was obtained (86% /follicle). The pregnancy rate after in vitro fertilization and embryo replacement was remarkably high (21.3%/cycle). Because exceptionally high-quality images of the organs in the pelvis are obtained, there are numerous other potential applications for the trans-vaginal sector scanner.

The use of synthetic culture medium and patient serum for human in vitro fertilization and embryo replacement.

The use of heat-inactivated patient serum as both fertilization and embryo replacement medium was compared in a prospective randomized study with a fully synthetic culture medium containing human serum albumin without serum addition (B3 INRA Menezo). Another series of the author's IVF program was analyzed retrospectively when a commercially available synthetic medium with bovine serum albumin (B2 INRA Menezo) or B3, as mentioned above, was used without serum addition for fertilization but with 50-100% patient serum as embryo replacement medium. Fertilization rates were significantly higher in the synthetic culture media (70%) than in serum (57%). The rate of polyploid fertilization was significantly lowest in B3 medium. There was a clear trend toward better pregnancy rates when high-percentage or 100% patient serum was used for embryo replacement, no matter if one, two, three, four or more embryos were replaced. We conclude that there should be no need for any kind of serum addition to fertilization media. The present study proves our previous observation that the use of serum seems to be beneficial as embryo replacement medium. This might well be explained by a "protein stick effect" due to the high macromolecular contents of serum rather than by viscosity measurements, since no significant increase in viscosity was observed when a high percentage of serum was added to culture media.

[Initial results of a cryopreservation program for human ova and embryos]. / Erste Ergebnisse eines Kryokonservierungsprogrammes menschlicher Eizellen und Embryonen.

A human egg and embryo freezing program for non fertilized eggs and spare embryos was established recently in our ib vitro fertilization clinic. The first results are reported. Two cryoprotectants, glycerol and dimethylsulfoxid (DMSO) were used in an automatic computerized freezing program. DMSO gave us better results in terms of a 55% survival of all blastomeres (from 6 normal and 5 pathologic 2- to 16-cell embryos) after thawing. Some of the thawed embryos continued cleavage in vitro. Four embryo replacements were performed with the 6 normal embryos, but none of them resulted in pregnancy. The rapid technique using glycerol gave us less good results in terms of blastomere survival (34%); however, from 3 embryo replacements one "biochemical pregnancy" was obtained from a thawed four-cell embryo. At first attempts to freeze and thaw unfertilized eggs, DMSO seemed also to give better results. The presented cryopreservation techniques which are modifications of those published by Trounson et al. and Zeilmaker et al. need further improvement although the first results are encouraging.