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Biomedical subjects

P Svalander

Publications and source records attributed to P Svalander.

12 recordsLinked to original sources

The outcome of intracytoplasmic sperm injection is unrelated to 'strict criteria' sperm morphology.

Sperm morphology was assessed according to the 'strict criteria' established for in-vitro fertilization treatment in the semen samples used for 354 consecutive treatment cycles for intracytoplasmic sperm injection (ICSI). The semen samples were classified according to the three predictive categories of the Tygerberg strict criteria: excellent prognosis (>14% morphologically normal spermatozoa), good prognosis (4-14%) and poor prognosis (<4%). It was found that 37 (10.5%) of the ICSI cycles belonged to the excellent prognosis category, 197 (55.6%) to the good prognosis category, and 120 (33.9%) to the poor prognosis category. The outcomes of the ICSI treatments were evaluated and compared with the sperm morphology classification in order to determine whether the strict criteria could aid in predicting the outcome of ICSI. The fertilization rates in the three categories were 61.6, 66.8, and 61.9%, the pregnancy rates per oocyte retrieval 18.9, 24.9, and 28.3%, and the implantation rates 9.9, 13.0, and 14.9% respectively. No significant differences were found in fertilization, pregnancy, or implantation rates between the three prognosis categories, i.e. the poor prognosis category had an equal chance of obtaining pregnancy compared with the good prognosis category. The results indicate that strict sperm morphology is not related to the outcome of ICSI.

Adult↗

Factors of importance for the establishment of a successful program of intracytoplasmic sperm injection treatment for male infertility.

OBJECTIVE: To establish an intracytoplasmic sperm injection treatment program for couples with male infertility and to determine those factors important for success. DESIGN: A retrospective analysis of 171 consecutive cycles of intracytoplasmic sperm injection concerning 145 infertile couples. SETTING: Infertility clinic in a private hospital associated with a university hospital. PATIENTS: Couples with infertility in the male partner whose sperm parameters were unacceptable for conventional IVF or in whom fertilization by conventional IVF failed repeatedly. INTERVENTIONS: One hundred seventy-one transvaginal oocyte retrievals were completed after superovulation with GnRH agonist and gonadotropins. MAIN OUTCOME MEASURES: The parameters evaluated included fertilization, cleavage, implantation, pregnancy, and spontaneous abortion in relation to patient indications and improved procedures. RESULTS: After intracytoplasmic sperm injection, normal fertilization occurred in 45% of the oocytes (n = 1,499). Of 171 treatment cycles, 93% of the couples had fertilization and 86% had ET. Thirty-six pregnancies were achieved. During the period studied, the mean fertilization rate increased from 21.3% during the first 17 weeks to 67.8% during the last 13 weeks, and the pregnancy rate (PR) per started cycle increased from 12.8% to 31.3%. CONCLUSIONS: Technical factors critical for achieving high rates of fertilization and pregnancy were the use of standardized intracytoplasmic sperm injection pipettes, the immobilization of sperm before injection, and the aspiration of a minimal amount of ooplasm before reinjection with the sperm. Intracytoplasmic sperm injection appears to be superior to other micromanipulation methods for alleviating male infertility.

Adult↗

Microfertilization techniques--the Swedish experience.

Intracytoplasmic sperm injection (ICSI) has been studied in this animal research programme since 1990. In 1993, the technique was first applied clinically and up to the present time (September 1994), a total of 456 couples have been studied in 538 cycles. The principal indication for the use of ICSI has been severe male sub-fertility as judged by a semen analysis. In addition, men with high titres of antisperm antibodies, blockage of the vas deferens and neurological disorders such as spinal cord lesions have been included in the programme. Men with genetic disorders such as cystic fibrosis and acrosome-deficient spermatozoa have also been treated successfully. The overall fertilization rate using ICSI was 59%, which is similar to the conventional in vitro fertilization (IVF) programme in Göteborg, however, the pregnancy rate per embryo transfer (29%) and the ongoing pregnancy rate per transfer (22%) were slightly lower. The total number of pregnancies was 144 with 111 of the pregnancies either ongoing or already delivered. To date, 36 healthy children have been born following 29 deliveries and no major malformations have been diagnosed. Being the first programme in Scandinavia to perform ICSI, this unit has experienced long waiting lists which indicates that severe male sub-fertility will be one of the major groups for treatment with assisted reproductive technologies in the future.

Cryopreservation↗

Human chorionic gonadotrophin self-administered by the subcutaneous route to induce oocyte maturation in an in-vitro fertilization and embryo transfer programme.

This study was initiated to evaluate oocyte maturation and the outcome of in-vitro fertilization (IVF) cycles following the s.c. administration of human chorionic gonadotrophin (HCG) by the patient herself or her partner. A group of 104 women who entered our IVF embryo transfer programme were prospectively randomized to have 5000 IU or 10,000 IU HCG s.c. or i.m. The HCG was administered for induction of the final oocyte maturation in cycles with pituitary down-regulation with a gonadotrophin-releasing hormone agonist according to a long protocol and where ovarian stimulation had been achieved with pure follicle stimulating hormone. The mean concentration of HCG in serum 12 and 36 h after the HCG injection was significantly higher in the women receiving 5000 IU i.m. compared to the s.c. route. However, in women receiving 10,000 IU HCG there were no significant differences in the mean concentrations 12 and 36 h after the injection, irrespective of the route of administration. Furthermore, there were no significant differences in the relative numbers of retrieved mature oocytes between the groups. When comparing the clinical outcome in the different groups, no significant differences were found between those receiving 5000 IU or 10,000 IU HCG, i.m. or s.c. Our data indicate that HCG can be given s.c. without reducing the chance of retrieving a mature oocyte and that the clinical outcome with regard to pregnancies is not negatively affected.

Adult↗

Subzonal insemination (SUZI) or in vitro fertilization (IVF) in microdroplets for the treatment of male-factor infertility.

PURPOSE: The results of subzonal insemination (SUZI) and in vitro fertilization with microdroplet insemination used in couples with male-factor infertility are presented. RESULTS: The total fertilization rate was 17.4% for SUZI (n = 89) and 49.3% for microdroplet IVF (n = 100). The fertilization rate for standard IVF (n = 510), not including any male-factor infertility and performed during the same period, was 73.2%. The "take-home baby rate" per started cycle and per embryo transfer (ET), respectively, was 10 and 17.6% for SUZI and 20 and 24.7% for microdrop IVF. For standard IVF these figures were 27 and 31.7%. CONCLUSION: It was concluded that microdroplet IVF can be used with good results in cases of moderate male-factor infertility. The normal (2PN) fertilization rate with the SUZI technique was only 15.1%. However, despite the low fertilization rate, SUZI should be considered when dealing with severe male-factor infertility.

Fertilization in Vitro↗

Effects of a single post-ovulatory dose of RU486 on endometrial maturation in the implantation phase.

The effect of a single post-ovulatory dose of RU486 on endometrial maturation was studied in the implantation phase. A total of 11 healthy women were followed for one control and one or two treatment cycles. In treatment cycles, a dose of 200 or 400 mg RU486 was administered on day luteinizing hormone (LH)+2. In both control and treatment cycles, an endometrial biopsy was obtained on LH+6 to LH+8. These biopsies were assessed by morphometric and immunohistochemical analyses. The treatment with RU486 did not disturb the normal menstrual rhythm but caused a significant inhibition in the endometrial development. Glandular progesterone receptor staining was significantly more pronounced after RU486 treatment, while there was a reduction in the Dolichos biflorus agglutinin lectin binding, indicating inhibition of the normal secretory transformation of the endometrium. It is likely that these effects on endometrial development and secretory activity represent the basis of the contraceptive effect of post-ovulatory RU486 treatment.

Adult↗

Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction.

During the past few years much effort has been put into simplifying the clinical management of in-vitro fertilization/embryo transfer cycles. One important step was the introduction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications of the clinical management of ovarian stimulation. During the period 1st January 1991 to 31st August 1993, three major simplification steps were introduced. All cycles were down-regulated with a gonadotrophin-releasing hormone (GnRH) agonist according to a long protocol permitting fairly precise programming of the oocyte collection. During period I (n = 329 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation. During period II (n = 230 cycles), only one ultrasound scan was used for monitoring the ovarian cycle; oocyte collections during weekends were avoided. During period III (n = 386 cycles), further simplification of the clinical management was introduced by using a highly purified follicle stimulating hormone (FSH) (Fertinorm/Metrodin HP), which was self-administered s.c. for ovarian stimulation. The take-home baby rates per started cycle for periods I, II and III were 16.4, 32.6 and 31.3% respectively. These figures indicate that when using long down-regulation with a GnRH agonist, simplification of the monitoring of the ovarian stimulation is possible without decreasing the pregnancy rate. Furthermore, the use of a highly purified FSH, self-administered s.c., greatly simplified treatment without compromising cycle outcome or increasing the risk of developing an ovarian hyperstimulation syndrome.

Adult↗

Effect of antihormones on endometrial receptors and protein secretion.

The antiestrogen tamoxifen and the antiprogestin RU 486 both interact with respective hormones at the receptor level, RU 486 as a pure antagonist which inhibits endometrial development, the downregulation of estrogen and progesterone receptors and the production of endometrial protein, such as PP14, during the secretory phase of the menstrual cycle. Tamoxifen, on the other hand, has both agonistic and antagonistic action.

Endometrium↗

Early luteal phase treatment with mifepristone (RU 486) for fertility regulation.

Mifepristone (RU 486) is an antiprogestin which interacts with progesterone at the receptor level. Administration of mifepristone immediately after ovulation does not upset the menstrual cycle. However, the maturation and function of the endometrium is inhibited and uterine contractility is changed. To test if these effects are sufficient to prevent implantation, 21 women agreed to use one single treatment with 200 mg mifepristone on day luteinizing hormone (LH) + 2 monthly as their only contraceptive method. The women were treated for 1-12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon). The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. In these cycles no treatment was given and the women advised to use barrier methods during the time to menstruation. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. One pregnancy occurred. On the basis of the time of the LH peak, it was retrospectively calculated that in 124 cycles at least one act of intercourse occurred during the period 3 days before to 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle is thus 0.008. The women did not complain of any treatment-related side-effects apart from slight bleeding for 2-3 days starting a few days after the day of treatment in 35% of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of an antiprogestin, mifepristone, and an antiestrogen, tamoxifen, on endometrial 17 beta-hydroxysteroid dehydrogenase and progestin and estrogen receptors during the luteal phase of the menstrual cycle: an immunohistochemical study.

The effects of a progesterone antagonist, mifepristone (RU486), and an estrogen antagonist, tamoxifen, given during the early luteal phase on endometrial 17 beta-hydroxysteroid dehydrogenase (17HSD) and estrogen (ER) and progesterone (PR) receptors were studied. Eleven regularly menstruating women were studied during control and treatment cycles. In the treatment cycle on day LH + 2 (2 days after the peak serum LH concentration), 10 subjects received a single dose of 200 mg mifepristone, and 9 received 2 doses of 40 mg tamoxifen on days LH + 2 and LH + 3. In addition, 4 subjects received 400 mg mifepristone in a separate treatment cycle. 17HSD, ER, and PR were measured immunohistochemically in endometrial tissue specimens taken on days LH + 6 to LH + 8. Blood samples were conducted during control and treatment cycles, and serum estradiol, progesterone, and LH concentrations were quantified by RIA. Administration of mifepristone blocked the induction of 17HSD by progesterone and prevented the expression of 17HSD in gland and surface epithelial cells in 8 patients. In 2 patients, staining of 17HSD was seen during both the control and mifepristone treatment cycles. The higher dose of mifepristone additionally given to four subjects did not block the expression of 17HSD in 2 cases where blocking was observed with the lower dose of mifepristone, and in 1 of these patients, very strong staining of 17HSD was observed in basal cells beneath the epithelial cells. ER and PR showed intense staining in the nuclei of both gland and stromal cells in mifepristone treatment cycles, whereas receptor staining was faint or absent in the respective control cycles. Tamoxifen did not have any significant effect on staining of 17HSD or the abundance of receptors. Serum concentrations of estradiol, progesterone, and LH were not significantly affected by the administration of mifepristone or tamoxifen. This study reveals that mifepristone, administered in the early luteal phase, usually blocks the expression of 17HSD and the down-regulation of PR and ER. However, the expression of 17HSD in some patients may reflect the ineffectiveness of the mifepristone treatment used to prevent implantation in certain subjects.

17-Hydroxysteroid Dehydrogenases↗

Mode of action of RU 486.

RU 486 is a 19-norsteroid which has a specific high affinity binding to the progesterone and glucocorticoid receptor. It is generally accepted that RU 486 acts as a pure progesterone antagonist almost without agonistic activity. RU 486 acts mainly directly on the target organ, such as the endometrium, but also to some extent indirectly through an effect on the pituitary gonadotrophin secretion. The effect of RU 486 during the menstrual cycle is dependent on time of treatment. Treatment before ovulation will result in a prolongation of the proliferative phase of the menstrual cycle, while treatment during the mid- and late luteal phase will invariably induce bleeding, often followed by a second bleeding episode at the expected time of menstruation. The only treatment period which does not influence the menstrual cycle is treatment immediately following ovulation. Treatment during the proliferative phase has no effect on endometrial morphology but inhibits follicular development and delays oestrogen and LH surge. Treatment on the first days following ovulation has no effect on ovarian steroid concentration, but will significantly delay endometrial development, cause a change in the concentration of oestrogen and progesterone receptor concentration enzyme activity and production of substances thought to be progesterone dependent. The change in endometrial development is sufficient to prevent implantation. In mid- and late luteal phase, treatment with RU 486 will result in endometrial shedding in spite of normal progesterone levels. Post-ovulatory treatment with RU 486 will also significantly change uterine contractility. In early pregnancy, withdrawal of progesterone inhibition will result in uterine contractility and a significant increase in the sensitivity of the myometrium to prostaglandin.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Induced↗