Håkan Wramsby

Chromosome Analysis of Human Oocytes Recovered from Preovulatory Follicles in Stimulated Cycles

Abstract To investigate the incidence and types of abnormalities of chromosome number in oocytes, we recovered preovulatory oocytes from 17 women who were undergoing clomiphene stimulation and laparoscopy because of infertility. Twenty-three oocytes were recovered and studied after they had been fixed with a gradualfixation method: 17 of the oocytes had numbers of chromosomes in the haploid range (19 to 25 second-metaphase chromosomes), 4 had only 1 to 5 chromosomes, 1 was not analyzable, and 1 had 23 chromosome bivalents in the first metaphase. Of the oocytes with chromosome numbers in the haploid range, nine had an apparently normal haploid set of 23 chromosomes. Two had 1 to 2 additional chromosomes, three lacked 2 to 4 chromosomes, and three had totals of chromosomes that were close to 23 but could not be determined with certainty. We conclude that infertile women undergoing clomiphene stimulation have a high proportion (nearly 50 percent) of oocytes with an abnormal karyotype. If this is also true of...

Personality factors and emotional responses to pregnancy among IVF couples in early pregnancy: a comparative study.

Background. Little is known as to whether negative experiences associated with infertility and IVF treatment persist after successful treatment. The aim of the study was to compare couples who have conceived after IVF and couples who have conceived naturally regarding personality factors and emotional responses to pregnancy.

Zona pellucida thickness variation and occurrence of visible mononucleated blastomeres in preembryos are associated with a high pregnancy rate in IVF treatment

Purpose: The ability of six morphological criteria (embryo development rate, fragmentation, regularity of blastomere shape, equality of blastomere size, zona pellucida thickness variation [ZPTV], and visible mononucleated blastomeres [VMBs]) to predict pregnancy in IVF treatment cycles was evaluated.Methods: In order to select a homogeneous study group, 85 consecutive nulliparous couples with single tubal infertility undergoing their first IVF treatment and receiving three preembryos at embryo replacement 2 days after ovum pickup were included.Results: A total of 255 preembryos was replaced two days after ovum pickup and resulted in 34 clinical pregnancies (40%). By logistic regression analysis, ZPTV and VMBs showed highly significant and strong predictive values, whereas none of the other parameters was a significant predictor of pregnancy. In the treatments in which all replaced preembryos had a ZPTV of less than 15%, the pregnancy rate was extremely low (1/22). If the maximum ZPTV of any of the replaced preembryos was in the interval between 15 and 20%, the pregnancy rate was 24.1% (7/29). In the treatments in which at least one preembryo had a ZPTV of more than 20%, the pregnancy rate was 76.5% (26/34). When VMBs were added to the results of the ZPTV analysis, the pregnancy rate was as high as 92.3% (24/26).Conclusions: ZPTV and VMBs seem to be strong predictors of pregnancy in IVF treatment and thus important indicators of good embryo quality.

Patterns of emotional responses to pregnancy, experience of pregnancy and attitudes to parenthood among IVF couples: a longitudinal study

The aim of this longitudinal study was to compare couples who had conceived by in-vitro fertilization (IVF) with couples who had conceived naturally, regarding patterns of emotional response to different stages of pregnancy and to compare their expectations of and attitudes to pregnancy, parenthood and children. Fifty-seven IVF women and 55 of their male partners, and a control group of 43 pregnant women and 39 of their male partners participated. They completed scales measuring emotional responses to pregnancy, attitudes to pregnancy, parenthood and children. The IVF couples were interviewed about their experience of pregnancy. The overall anxiety about losing the pregnancy was higher among the IVF couples from early to late pregnancy. The IVF women experienced the pregnancy in a more positive way and they were less concerned about the childs gender and loss of freedom in their future lives as parents compared to controls. The IVF men were more anxious about the baby being injured during birth. The interviews with the IVF couples confirmed the self-ratings. In conclusion, the results suggest that it is important for healthcare providers to pay attention to an elevated anxiety among IVF couples and to give them extra time to discuss emotions during pregnancy and their future life as parents.

Transforming growth factor-β1, insulin-like growth factors, and insulin-like growth factor binding proteins in ovarian follicular fluid are differentially regulated by the type of ovarian hyperstimulation used for in vitro fertilization

OBJECTIVE To determine the effects of hMG and highly purified FSH on follicular production of the ovarian growth factors transforming growth factor-beta1 (TGF-beta1), insulin-like growth factors I and II (IGF-I and IGF-II), and insulin-like growth factor binding proteins-1 and -3 (IGFBP-1 and IGFBP-3). DESIGN Controlled clinical study. SETTING University IVF program. PATIENT(S) One hundred twenty women who were <38 years old and had a >3-year duration of infertility in their present relationship participated in the study. INTERVENTION(S) Follicular fluid and matched serum were collected at oocyte pick-up and analyzed for growth factors and E2 with the use of ELISA and RIA. MAIN OUTCOME MEASURE(S) Levels of TGF-beta1, IGF-I. IGF-II, IGFBP-1 and IGFBP-3 in follicular fluid and levels of E2 in serum were measured. RESULT(S) Compared with highly purified FSH, ovarian hyperstimulation with hMG produced lower levels of TGF-beta1 and IGF-I and higher levels of IGFBP-1. Levels of IGF-II and IGFBP-3 were similar with the 2 treatments. CONCLUSION(S) In patients undergoing IVF, the follicular expression of TGF-beta1, IGF-I, and IGFBP-1 was regulated differently by highly purified FSH compared with a preparation containing FSH and LH in a 1:1 ratio (hMG). The results indicate that FSH and LH control ovarian production of these growth factors differentially.

Controlled ovarian stimulation using highly purified FSH results in a lower serum oestradiol profile in the follicular phase as compared with HMG

We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.

Selection of ovarian stimulation protocol is related to IVF treatment outcome in women 35 years of age and older

PurposeThe aim of this study was to assess if the womans age influenced IVF treatment outcome when a long GnRHa-hMG or a CC-hMG ovarian stimulation protocol was used. Two hundred women were included in the study, 100 women under the age of 35 and 100 women 35 years of age and older (mean 31.8 years and 36.7 years respectively). In the younger group as well as in the older group 50 women were stimulated according to a GnRHahMG protocol and 50 women received a CC-hMG regimen.ResultsSignificant differences between stimulation protocols were found in the older group for the mean numbers of oocytes recovered (4.7 vs 3.0), preembryos obtained (3.2 vs 2.0) and replaced (2.3 vs 1.7), as well as pregnancy (30 % vs 10 %) and delivery (24 % vs 4 %) rates per replacement.ConclusionIt is concluded that women over 35 years of age seem to have a more favorable outcome of IVF treatment when using a long GnRHa-hMG protocol compared with CC-hMG, while this difference was not as obvious and lacking statistical significance under the age of 35.

Endometrial Evaluation Is Not Predictive for In Vitro Fertilization Treatment

Purpose:The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome.Methods and Results:Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant.Conclusions:Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome.

Importance of endometrial quality in women with tubal infertility during a natural menstrual cycle for the outcome of IVF treatment.

Purpose: The importance of endometrial maturation at estimated time of implantation for the outcome of IVF treatment in regularly menstruating women with tubal infertility was evaluated.Methods: FSH was measured on cycle day 3, on days 10–15 urine and blood were collected to estimate the day of the LH peak, and E2 and P4 were measured during the luteal phase, on cycle days 19–26. An endometrial biopsy was obtained on days LH + 3 to LH + 6.Results: The number of subjects with delayed endometrial maturation was larger in the group of infertile women who did not become pregnant compared to pregnant women and controls. Those infertile women who did not become pregnant after IVF treatment also presented with a higher basal FSH on cycle day 3 and lower E2 and P4 AUC in the luteal phase. Six infertile women and two controls presented with mid- and late-proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in the presence of adequate E2 and P4 secretion. Six morphological characteristics were compared in the three groups: (1) 17 infertile women who became pregnant, (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile women did not differ from the controls. The numbers of glandular and stromal mitoses were significantly higher in those women who did not become pregnant (P<0.01) compared with those who became pregnant. Endometrial biopsies obtained on cycle days LH + 5 and LH + 6 showed significant differences in glandular epithelial height (P<0.05) and number of vacuolated cells among the nonpregnant women (P<0.01), the pregnant women (P<0.05), and controls.Conclusions: A higher frequency of retarded endometrial development in women who did not become pregnant following IVF treatment was found. In some cases, endometrial insensitivity could most likely cause retarded endometrial development and failure of implantation after IVF treatment, which could not be overcome by routine luteal-phase support. However, our results do not allow conclusions concerning its relative importance compared to preembryo quality; this has to be investigated further.

Ovarian function in relation to the outcome of in vitro fertilization (IVF) treatment in regularly menstruating women with tubal infertility

Study DesignOvarian endocrine function was evaluated in 53 regularly menstruating women, 27 to 38 years of age, who failed to conceive at least 2 years following reconstructive surgery for tubal infertility. Thirty apparently healthy women, 24 to 40 years of age with proven fertility, served as controls. Blood samples were obtained daily on cycle days 2–4 and 22–26 to assess FSH, E2, and P4 levels.ResultsThere was a tendency for women with more advanced tubal damage to be subjected to more extensive surgery. Based on extent of reconstructive surgery, the patients were divided into three groups. Group A (n=29) had less extensive surgery, limited to the fallopian tubes, group B (n=14) included patients with extended adhesiolysis, and group C (n=10) comprised patients that had the most extensive reconstructive procedures involving ovarian surgery. Significantly higher FSH levels were found in group C (P<0.001) compared to groups A and B in the early follicular phase. During the luteal phase, E2 levels were lower in groups B (P<0.01) and C (P< 0.001) compared to group A. P4 levels were lower in group C compared to groups A and B.ConclusionWhen the patients underwent IVF treatment higher grades of tubal damage, more extensive surgery and hormonal signs of ovarian insufficiency were highly related to treatment failure.