Using anti-Müllerian hormone to identify a good prognosis group in women of advanced reproductive age.

BACKGROUND: The probability of pregnancy after in vitro fertilisation (IVF) declines with age in parallel with a reduction in the ovarian reserve. However, there is considerable variation in the ovarian reserve in women of advanced reproductive age; so to give such women accurate advice about the prospects of treatment success, factors other than age must be considered. Anti-Müllerian hormone (AMH) has been shown to be a good indicator of ovarian reserve, and its utility is explored in this paper. AIMS: To determine the utility of AMH serum levels for prediction of ovarian response to gonadotropin stimulation and outcome in IVF in women of advanced reproductive age. METHODS: The material consists of 127 women with a median age of 42 years (range 39-46) having had their first cycle of IVF/intracytoplasmic sperm injection (ICSI) treatment from November 2006 to December 2008. During this period, a total of 772 oocyte retrievals and 715 embryo transfers were performed at the clinic (median age 36.4 years). AMH was analysed with the Beckman Coulter DSL ELISA. Agonist and antagonist protocols were used and monitored by ultrasound and oestradiol; embryo transfer was performed on day 2, 3 or 5 of culture. RESULTS: The lower the AMH, the higher the risk of cycle cancellation, low oocyte yield and treatment failure. Women with a serum AMH above 8.6 pmol/L had a good chance of achieving live birth after IVF/ICSI treatment. CONCLUSIONS: Anti-Müllerian hormone is useful for identifying a good prognosis group in women of advanced reproductive age.

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.

Extracellular matrix of the human cyclic corpus luteum.

Extracellular matrix regulates many cellular processes likely to be important for development and regression of corpora lutea. Therefore, we identified the types and components of the extracellular matrix of the human corpus luteum at different stages of the menstrual cycle. Two different types of extracellular matrix were identified by electron microscopy; subendothelial basal laminas and an interstitial matrix located as aggregates at irregular intervals between the non-vascular cells. No basal laminas were associated with luteal cells. At all stages, collagen type IV alpha1 and laminins alpha5, beta2 and gamma1 were localized by immunohistochemistry to subendothelial basal laminas, and collagen type IV alpha1 and laminins alpha2, alpha5, beta1 and beta2 localized in the interstitial matrix. Laminin alpha4 and beta1 chains occurred in the subendothelial basal lamina from mid-luteal stage to regression; at earlier stages, a punctate pattern of staining was observed. Therefore, human luteal subendothelial basal laminas potentially contain laminin 11 during early luteal development and, additionally, laminins 8, 9 and 10 at the mid-luteal phase. Laminin alpha1 and alpha3 chains were not detected in corpora lutea. Versican localized to the connective tissue extremities of the corpus luteum. Thus, during the formation of the human corpus luteum, remodelling of extracellular matrix does not result in basal laminas as present in the adrenal cortex or ovarian follicle. Instead, novel aggregates of interstitial matrix of collagen and laminin are deposited within the luteal parenchyma, and it remains to be seen whether this matrix is important for maintaining the luteal cell phenotype.

Gonadotrophin-releasing hormone-antagonist luteolysis during the preceding mid-luteal phase is a feasible protocol in ovarian hyperstimulation before in vitro fertilization.

BACKGROUND: The aims of this study were to investigate whether a high dose of gonadotrophin-releasing hormone antagonist during the preceding luteal phase yields satisfactory luteolysis and downregulation prior to ovarian hyperstimulation in an in vitro fertilization program. METHODS: The treatment protocol was designed as a prospective pilot study in IVF units at two university hospitals. Fifty-one patients with documented poor or normal response to ovarian stimulation underwent 57 treatment cycles. Treatment consisted of 3 mg gonadotrophin-releasing hormone antagonist (cetrorelix) given during the preceding mid-luteal phase as gonadotrophin-releasing hormone-receptor inhibition before ovarian stimulation with follicle-stimulating hormone. RESULTS: All women experienced menstrual bleeding within 2-3 days after the injection of 3 mg cetrorelix. Follicle hormone stimulation could subsequently commence in all cycles. All but three patients developed growing follicles and underwent oocyte retrieval. Seventy-five percent of started cycles reached transfer of one or two good-quality embryos. CONCLUSIONS: A single high-dose gonadotrophin-releasing hormone antagonist given during the preceding luteal phase presents a new and feasible protocol to initiate controlled ovarian hyperstimulation in an in vitro fertilization program.

Birth of a healthy infant after in vitro oocyte maturation and ICSI in a woman with diminished ovarian response: case report.

In vitro maturation of oocytes (IVM) has been developed as a treatment option for subjects with good prognosis in assisted reproduction. We present successful IVM treatment in connection with a woman from whom low numbers of embryos were obtained after repeated failed conventional IVF cycles. A 35 year old woman, after 5 years infertility and two intrauterine insemination and three conventional IVF cycles, underwent first an IVM cycle with low dose FSH stimulation, and after failure, another natural IVM cycle. Three oocytes were obtained. After 36 h of IVM the oocytes had reached metaphase II stage, and fertilization using ICSI resulted in one 4-cell stage embryo, which was transferred 2 days later. The result was an uneventful pregnancy and birth of a healthy female infant weighing 4150 g. IVM may be an option for women from whom only low numbers of oocytes are obtained after gonadotrophin stimulation.

Why do couples discontinue in vitro fertilization treatment? A cohort study.

OBJECTIVE: To investigate reasons for discontinuation of IVF treatment. DESIGN: Prospective, cohort study. SETTING: Center for reproductive medicine at a large university hospital. PATIENT(S): The 450 couples of a cohort of 974 couples who started IVF treatment between January 1996 and December 1997 and did not achieve childbirth. INTERVENTION(S): The reasons for ceasing treatment were evaluated by scrutinizing the medical records for all couples (n = 288) who did not achieve live birth and who did not complete three stimulated IVF cycles. A questionnaire was sent to all patients for whom the reason for discontinuation was not obvious from the medical records (n = 211). MAIN OUTCOME MEASURE(S): Reasons for discontinuing IVF. RESULT(S): Of 450 couples not achieving live birth, 208 completed their subsidized cycles, whereas 242 discontinued IVF. In 192 (79%) of the 242 cases, the reasons for ceasing treatment could be identified from records or questionnaires. The reason for discontinuation was psychological burden in 26%, a poor prognosis in 25%, spontaneous pregnancy in 19%, physical burden in 6%, serious disease in 2%, and other reasons in 7%. CONCLUSION(S): An unexpectedly high percentage of couples who performed IVF discontinued the treatment before the three cycles that were offered to a majority of the couples. A majority of these discontinuations were due to psychological stress. This information is of importance when counseling patients during treatment.

Psychological aspects of discontinuation of in vitro fertilization treatment.

A considerable number of patients discontinue in vitro fertilization treatment because of psychological reasons.

Recombinant LH is equally effective as recombinant hCG in promoting oocyte maturation in a clinical in-vitro maturation programme: a randomized study.

BACKGROUND: Fertilization treatment using oocytes matured in vitro from pre-ovulatory follicles has many potential applications. It minimizes the risk of severe ovarian hyperstimulation and is an alternative for women with polycystic ovary syndrome who may have problems regarding stimulation for IVF. In-vitro maturation (IVM) may prove important for subjects needing fertility preservation, and also provides information about the final stages of oocyte maturation. METHODS: From a randomized study of 73 women in an IVF programme, 36 subjects with 228 oocytes were allocated for oocyte maturation in culture medium with recombinant hCG, and 37 subjects with 256 oocytes for maturation with recombinant LH. The primary outcome was the rate of nuclear maturation of oocytes to metaphase II. During the same period, 32 women outside the study underwent 38 individually tailored IVM treatments. RESULTS: The oocyte maturation rate was 54.8% with hCG and 55.9% with LH; fertilization and cleavage rates were not significantly different. Three pregnancies were achieved in the hCG group and one in the LH group. Seven pregnancies (22.6% per embryo transfer) were achieved in the parallel group. CONCLUSIONS: Recombinant hCG or LH are equally effective in promoting oocyte maturation in a clinical IVM programme.

Expectant management of first-trimester miscarriage in clinical practice.

BACKGROUND: The aim of this study was to evaluate treatment efficacy and patient compliance in women with an early miscarriage managed expectantly in routine clinical practice. METHODS: During 1995-98, 263 consecutive women who sought medical attention for an ongoing or incomplete miscarriage (gestational length <99 days), and who were circulatory stable and had a gestational residue measuring 15-50 mm (anterio-posterior, A-P diameter) on ultrasound examination were invited to participate in this study. Hemoglobin (Hb), C-reactive protein (CRP), human chorionic gonadotrophin (hCG), progesterone and Rh-factor were analyzed and a questionnaire regarding the pregnancy, duration of genital bleeding and number of days of absenteeism was completed on admission and after 1 and 4 weeks. RESULTS: Expectant management was considered to be complete (vaginal ultrasound, gestational residue <15 mm after 1 week) in 83%. The patients who were managed successfully by expectant management had a smaller gestational residue (p = 0.026) and a lower mean serum progesterone level (p = 0.025) on referral than in the group of women with failed expectant management. A gynecologic infection was diagnosed in seven cases (3%) and five of the infections were in the group of women who underwent dilatation and curettage. No patient required a blood transfusion. The mean number of days of absenteeism was 3.2 days. There were no differences in Hb levels before or after treatment, number of bleeding days or absenteeism between the groups. CONCLUSIONS: Expectant management of clinically stable patients with symptoms of early miscarriage is safe, efficient and well tolerated.

Cumulative probability of live birth after three in vitro fertilization/intracytoplasmic sperm injection cycles.

OBJECTIVE: To assess the probability of live birth after three available in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. DESIGN: Retrospective, observational study. SETTING: University hospital. PATIENT(S): Nine hundred seventy-four couples who started their first conventional IVF or ICSI cycle between January 1996 and December 1997. A total of 1985 stimulated cycles were initiated. INTERVENTION(S): Analysis of the cumulative live birth rate using the life-table approach with and without taking dropouts into account. MAIN OUTCOME MEASURE(S): Cumulative live birth rate. RESULT(S): The overall cumulative live birth rate after three completed stimulated cycles (including freezing/thawing cycles) was 65.5% with an "optimistic" approach. For the "realistic" and "pessimistic" approaches the corresponding figures were 63.1% and 55.5%, respectively. Unexpectedly, 65% of couples not achieving a live birth interrupted the full treatment program of three cycles. CONCLUSION(S): The cumulative live birth rate gives the couple a more accurate prognosis of achieving a live birth after IVF/ICSI than the statistics usually provided. With the "realistic" estimation, 63% of the couples achieved childbirth after three available conventional IVF or ICSI cycles. Further studies are required to investigate the high drop-out rate.