Predictive value of hormonal parameters for live birth in women with unexplained infertility and male infertility.

BACKGROUND: Infertile women might get pregnant sometime after fertility treatment, but today, there is no prediction model on who will eventually have children. The objective of the present study was to characterize hormone levels in an arbitrary menstrual cycle in women with unexplained infertility and male infertility, and to determine the predictive value for long-term possibility of live birth. METHODS: In this cross-sectional study, with 71 infertile women with diagnosis unexplained infertility and male infertility, blood samples were obtained during the proliferative and secretory phases of an arbitrary menstrual cycle. Serum concentrations of FSH, LH, AMH, inhibin B, estradiol, progesterone, PRL and TSH were determined. The predictive value of ovulation and hormonal analysis was determined by identifying the proportion of women with at least one live birth. Mann Whitney U test, chi2 test and Spearman's correlation were used for statistical analysis. A value of p < 0.05 was considered statistically significant. RESULTS: There were no differences in hormone values and live birth rates between women with unexplained infertility and male infertility. The best sole predictors of live birth were age of the women, followed by ovulatory cycle, defined as serum progesterone concentration of greater than or equal to 32 nmol/L, and a serum TSH concentration of less than or equal to 2.5 mIU/L. Combining the age with the ovulatory cycle and serum TSH less than or equal to 2.5 mIU/L or serum AMH greater than or equal to 10 pmol/L the predictive value was close to 90%. CONCLUSIONS: Age in combination with the presence of an ovulatory cycle and serum TSH or serum AMH is predictive for long-term live birth. The advantage of serum AMH compared with serum TSH is the very little variation throughout the menstrual cycle, which makes it a useful tool in infertility diagnosis.

Tissue factor and tissue factor pathway inhibitors TFPI and TFPI2 in human secretory endometrium--possible link to female infertility.

The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.

Luteal phase progesterone increases live birth rate after frozen embryo transfer.

OBJECTIVE: To see if progesterone support has a beneficial effect on live birth rate after frozen embryo transfer in natural cycles. DESIGN: Prospective randomized controlled trial. SETTING: University-based hospital. SUBJECT(S): Four hundred thirty-five women undergoing embryo transfer in natural cycles. INTERVENTION(S): The women received either vaginal progesterone, 400 mg twice a day from the day of embryo transfer in natural cycles, or no progesterone support. MAIN OUTCOME MEASURE(S): Live birth rate, biochemical pregnancy rate, pregnancy rate, and spontaneous abortion rate. RESULT(S): Live birth rate were significantly greater in women receiving vaginal progesterone as luteal phase support after frozen-thawed embryo transfer in natural cycles compared with those who did not take progesterone. There were no differences in biochemical pregnancy rate, pregnancy rate, or spontaneous abortion rate. CONCLUSION(S): Progesterone supplementation improves live birth rate after embryo transfer in natural cycles.

Disturbances in the LIF pathway in the endometrium among women with unexplained infertility.

OBJECTIVE: To study the expression of leukemia inhibitory factor (LIF), its receptors LIFR and gp130, and its inhibitor SOCS1 in endometria from fertile women and infertile women with unexplained infertility. Signaling through the LIF pathway is involved in maintenance of a receptive state of human endometrium. Impaired endometrial receptivity may be a cause of female infertility. DESIGN: Prospective clinical study. SETTING: Hospital-based IVF unit and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-six healthy fertile women and 14 women with unexplained infertility. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Pinopode formation, expression of LIF, LIFR, gp130, and SOCS1 protein and mRNA in endometrial biopsies. RESULT(S): The expression of LIFR in the endometrium was negatively correlated to the expression of SOCS1 and positively correlated to the formation of pinopodes. In control fertile women, simultaneous intense apical staining of LIFR and gp130 together with faint SOCS1 staining was observed in epithelial cells, whereas the opposite was seen in most women with unexplained infertility. CONCLUSION(S): Unexplained infertility in some women might be explained by disturbances in the LIF pathway in midsecretory-phase endometrium.

HB-EGF but not amphiregulin or their receptors HER1 and HER4 is altered in endometrium of women with unexplained infertility.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its receptors (HER1 and HER4) play a role in the human implantation process. Amphiregulin is a member of the EGF family but with unknown function in human fertility. It has been suggested that some women with unexplained infertility have defective endometrial development. The aim of this study is to determine the presence of amphiregulin and the receptors HER1 and HER4 in normal human endometrium throughout the menstrual cycle. In addition, the present study aims to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of HB-EGF, HER1, HER4, and amphiregulin. The stromal staining of HER1 and the epithelial staining of HER4 were most intense in the mid- and late-secretory-phase endometrium. Amphiregulin did not vary during the menstrual cycle. In the mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility versus normal endometrium and endometrium from women with male factor infertility. HB-EGF and HER4 mRNA expression in mid-secretory endometrium of women with unexplained and male factor infertility were increased compared with normal controls. Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility.

A new rapid and effective method for treatment of unexplained infertility.

BACKGROUND: Artificial insemination (intrauterine insemination by husband or artificial insemination by husband) is often tried as first treatment for couples with unexplained infertility. Pertubation has previously proved to increase the chance of achieving pregnancy for these couples. The effect of pertubation on fertility can be mechanical as well as anti-inflammatory by using a substance that inhibits phagocytosis of the spermatozoa.The objective of the study was to investigate the effect on pregnancy rate of pre-ovulatory pertubation with low-dose lignocaine during clomiphene citrate and insemination cycles for couples with unexplained infertility. METHODS: Ina prospective, open study, the patients were randomized, the day before ovulation, during a clomiphene citrate stimulated cycle to either pertubation with low-dose local anaesthetic or no pertubation before insemination. RESULTS: A total of 130 cycles were studied, 67 of which were randomized to pre-ovulatory pertubation and 63 to no pertubation treatment. There were 14.9% (n 5 10) clinical pregnancies in the pertubated group compared with 3.2% (n 5 2) in the group without pre-ovulatory pertubation (P < 0.05). CONCLUSIONS: The pertubation treatment significantly enhanced the clinical pregnancy rate and was well tolerated. No complications were noted. The combined treatment of clomiphene citrate, pertubation and insemination can be used as a cost-effective, first-line treatment for couples with unexplained infertility.

Exclusion of coding-region mutations in luteinizing hormone and follicle-stimulating hormone receptor genes as the cause of ovarian hyperstimulation syndrome.

OBJECTIVE: To sequence the coding regions of the luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) genes to find out if polymorphisms in them are responsible for the severe form of ovarian hyperstimulation syndrome (OHSS) in Swedish patients. DESIGN: A mutation analysis of gonadotropin receptor genes from women undergoing gonadotropin treatment. SETTING: The Fertility Unit of Karolinska University Hospital Huddinge, Stockholm, Sweden. PATIENT(S): A set of 10 well-characterized patients with severe OHSS, and 10 control women who did not develop OHSS after FSH stimulation. An additional 11 patients and 41 control women were screened for a two-amino-acid insertion in the first exon of the LHR gene. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Changes in the sequence of the receptor genes between patients and controls. RESULT(S): No association was found between polymorphisms of the coding region of LHR or FSHR genes and the development of OHSS. Incidence of the two-amino-acid insertion in the first exon of the LHR gene was slightly higher in patients than in controls, but no statistically significant difference was seen. CONCLUSION: LHR and FSHR coding polymorphisms are not a major cause of severe OHSS in Swedish patients.

Donation of embryos for stem cell research--how many couples consent?

BACKGROUND: The huge potential of human embryonic stem cells has been a subject of wide discussion as regards the ethical and legal justification of using human embryos for establishing such cell lines. The opinions of infertile couples and their willingness to donate their supernumerary embryos for stem cell research have not been investigated earlier. METHODS: We conducted an analysis of the answers of couples who were asked to give informed consent as regards donating their embryos for stem cell research in our IVF unit in 2001-2002. RESULTS: Ninety-two percent of the couples gave informed consent as regards establishing and characterizing embryonic stem cell lines from the embryos which could not be used in their infertility treatment. Discussion in the Swedish media during May to December, 2001 regarding the importance and ethical justification of stem cell research made informing the couples easier. CONCLUSION: A high proportion, 92%, of couples who underwent infertility treatment in Sweden preferred donating their supernumerary embryos for stem cell research rather than letting them be discarded.

Embryo transfer by midwife or gynecologist: a prospective randomized study.

BACKGROUND: Embryo transfer (ET) in assisted reproduction treatments has traditionally been performed by gynecologists in the Nordic countries. As gynecologists often have a busy schedule, midwives and nurses have become increasingly important in performing the treatment, providing subject information, ultrasound monitoring and assistance at ET. As part of the continuous development of our IVF treatment we have carried out a prospective randomized pilot study where either a midwife or a gynecologist has performed ET. The aim of this study was to see if a skilled IVF midwife could perform ET with similar results to a gynecologist. METHODS: On the day of oocyte aspiration the subjects were randomized, by means of closed envelopes, for ET to be performed either by a midwife or a gynecologist. A total of 102 subjects were included in the study, 51 for ET by a skilled midwife and 51 by a gynecologist. There were no differences in the groups in respect to ET routine and catheters used. RESULTS: No significant differences were observed in subject characteristics as regards age, method of pituitary down-regulation or proportion of IVF/ICSI cycles. Similar clinical pregnancy rates between ETs performed by midwives vs. gynecologists, 31% vs. 29%, respectively, were seen. Subject experience as judged by a questionnaire also showed high acceptance of ET by a midwife. CONCLUSION: The results show that it is a feasible option to allow midwives to carry out ETs.