Morphology of vitrified/warmed day-5 embryos predicts rates of implantation, pregnancy and live birth.

Although some post-thaw morphological predictors of pregnancy have been investigated in slow freezing of blastocysts, no such data have been published for vitrified and warmed blastocysts. Therefore, a prospective four-part score was applied to vitrified/warmed day-5 embryos to evaluate whether certain morphological parameters could serve as predictors of implantation, pregnancy and live birth. All morulae/blastocysts that were considered to be viable after warming were scored according to a previously unpublished grading system based on re-expansion, hatching (out of an artificial gap in the zona pellucida), extensive cytoplasmic granulation and presence of necrotic foci. Overall, 74% (202/273) of the vitrified concepti were found to be viable after warming. Early blastocysts showed better survival versus extended/hatching blastocysts (P < 0.01). Of the morphological parameters analysed, immediate re-expansion (P < 0.05) and hatching (P < 0.001) were positive predictors of the rates of implantation, pregnancy and live birth. The opposite holds for extensive cytoplasmic granulation (P < 0.05), which was negatively related. Accurate scoring of warmed blastocysts (within the first 2 h) allows for prediction of pregnancy outcome, and thus will help to further reduce the number of transferred embryos.

[Multiple pregnancies after ART: problems and possible solutions]. / Mehrlingsschwangerschaften nach ART: Probleme und Losungsansatze.

Multiple pregnancies following an assisted reproduction technique (ART) should be seen as a complication, and for that reason they should be avoided. In contrast to singleton pregnancies following ART, the multiple pregnancies are associated with a higher prenatal, neonatal and maternal risk; furthermore this results in a financial burden for the health care system. This paper gives an overview of the latest literature and different attempts of European countries, trying to reduce the multiple pregnancy rate. An efficient reduction is only possible by single-embryo transfers. There should be strict and cross-national regulation for the choice of women who should have a transfer of more than one embryo.

[Possibilities and limits of the quantitative demonstration of protein thiols with the DDD-reagent in cells of cervical epithelium (author's transl)]. / Möglichkeiten und Grenzen der quantitativen Bestimmung von Protein-Thiolen mit dem DDD-Reagens in Cervix-Epithelien.

From six patients, all with invasive carcinoma of the cervix uteri, two groups fo smear preparations, each consisting of eight samples, were taken: The first, group A, before and the second, group B, after mechanical removal of the discharge which was present in abundant quantities. All samples were treated for 24 h with DDD to reach the fast-reaching SH-groups, coupled with Fast Blue B and measured cytophotometrically at 560 nm. Without any exception, the neoplastic cells of group A showed significantly lower extinction values both of the nucleus and of the total cell, if compared to group B. The mean extinction difference amounts to 55% and is highly significant and some evidence is given that the viability of the cells plays an important role. For this reason, the quantitative evaluation of the DDD Fast Blue B does not seem to be useful for cytologic routine investigations.

Interactions between insulin and insulin-like growth factor I in the pathogenesis of polycystic ovarian disease.

Concentrations of growth factors were examined in 28 patients with clinical and endocrinologic signs of polycystic ovarian disease (PCOD). Elevated levels of total insulin-like growth factor I (IGF-I) and decreased levels of the human growth hormone (HGH) were found. Studies of carbohydrate metabolism and of insulin receptors on erythrocytes indicated insulin resistance in all PCOD patients. Elevated insulin and IGF-I levels seem to play a pathogenetic role in PCOD by influencing the development and steroid production of ovarian follicles. Interactions between insulin and IGF-I could be shown at different levels. A positive correlation between elevated insulin and IGF-I concentrations was demonstrated in patients with different classes of gestational diabetes. Hyperinsulinemia seems to be the trigger mechanism and therefore the key to the pathogenetic loop of polycystic ovarian disease.

Severe bleeding from peritoneal implants of trophoblastic tissue after laparoscopic salpingostomy for ectopic pregnancy.

OBJECTIVE: To describe a case of persistent trophoblastic tissue after conservative laparoscopic treatment of an ectopic pregnancy (EP). DESIGN: Case report. SETTING: University hospital. PATIENT: A 19-year-old nulliparous woman, presenting 30 days after conservative laparoscopic treatment of an EP. INTERVENTION(S): Emergency laparotomy, histologic examination of excised trophoblastic tissue, serial beta-hCG levels. MAIN OUTCOME MEASURE(S): Serum beta-hCG clearance curves after surgical treatment of an EP. RESULT(S): Histology confirmed multiple peritoneal implants of trophoblastic tissue, mainly situated on the sigmoid colon and the omentum majus. Serial beta-hCG levels decreased rapidly from 1,394 to 0 mU/L within 17 days. CONCLUSION(S): After conservative treatment of EP, patients should be followed up clinically and serial beta-hCG measurements should be obtained to ensure the absence of persistent trophoblastic tissue.

Controlled ovarian hyperstimulation in assisted reproduction: effect on the immune system.

OBJECTIVE: To determine how controlled ovarian hyperstimulation (COH) in assisted reproduction affects the immune system. DESIGN: A prospective, nonrandomized, case-control study. SETTING: Academic research setting. PATIENT(S): Women with regular menstrual cycles undergoing COH in an assisted reproduction program. INTERVENTION(S): Blood samples were collected in the early and late follicular phase, at the time of ovulation, and in the luteal phase during a natural cycle, and at four times during the next cycle, which included COH and IVF. MAIN OUTCOME MEASURE(S): Lymphocyte subpopulations and the differential blood count. RESULT(S): In the natural cycles, a significant increase in the total numbers of lymphocytes, B cells, natural killer cells, and CD3+HLADR+ cells was observed in the late follicular phase, whereas the T helper/T suppressor cell ratio declined. In the hyperstimulated cycles, increases were seen in the total numbers of leukocytes and neutrophils on the day of hCG administration; the number of lymphocytes, monocytes, and neutrophils was increased on the day of oocyte retrieval, and the total number of leukocytes and neutrophils increased during the luteal phase. CONCLUSION(S): Controlled ovarian hyperstimulation with hMG and simultaneous administration of a GnRH antagonist did not affect the immune system.

Subcutaneous adipose tissue pattern in lean and obese women with polycystic ovary syndrome.

The new optical device, Lipometer, permits the noninvasive, quick, safe, and precise measurement of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe the SAT topography (SAT-Top) like an individual "fingerprint." SAT-Top was examined in 33 women with polycystic ovary syndrome (PCOS), in 87 age-matched healthy controls and in 20 Type-II diabetic women. SAT-Top differences of these three groups were described, and, based on a hierarchical cluster analysis, two distinctly different groups of PCOS women, a lean (PCOS(L)) and an obese (PCOS(O)) cluster, were found. For visual comparison of the different types of body fat distribution, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. For comparison of the PCOS like body fat distribution with the "healthy" fat pattern, the (previously published) SAT-Top results of 590 healthy women and men (20-70 years old) and 162 healthy girls and boys (7-11 years old) were added to the factor plot. PCOS(O) women showed a SAT-Top pattern very similar to that of women with Type-II diabetes, even though the diabetic women were on average 30 years older. Compared with their healthy controls, SAT-Top of these PCOS(O) patients was strongly skewed into the android direction, providing significantly decreased leg SAT development and significantly higher upper body obesity. Compared with healthy women, PCOS(L) patients had significantly lower total SAT development (even though height, weight, and body mass index did not deviate significantly), showing a slightly lowered amount of body fat in the upper region and a highly significant leg SAT reduction. This type of fat pattern is the same as found in girls and boys before developing their sex specific body fat distribution. We conclude that women with PCOS develop an android SAT-Top, but compared in more detail, we found two typical types of body fat distribution: the "childlike" SAT pattern in lean PCOS patients, and the "diabetic" body fat distribution in obese PCOS women.

Insulin binding to erythrocytes of nonpregnant women: a reevaluation, underlining the importance of body weights even in nonobese subjects.

Insulin binding to erythrocytes was measured in 18 healthy, non-obese women in the follicular phase and in 6 women in the mid-luteal phase of the same menstrual cycle. The presence of 55 nM and 220 nM monoclonal anti-IGF I receptor antibody (alpha-IR3) reduced only the number of low affinity binding sites for insulin by 20% and 33%, respectively. Women with relative body weights 110-119% had a lower number of high affinity receptors and an increased high affinity compared to women with relative body weights 91-109%. In women with relative body weights greater than or equal to 100%, maximum specific binding and high affinity constants increased and the receptor numbers decreased from the follicular to the luteal phase, whereas in women with relative body weights less than 100% the parameter changes were reverted. The data indicate: (1) erythrocytes contain two different classes of binding sites for insulin, (2) IGF I receptors might contribute to low-affinity binding of insulin to erythrocytes and (3) the relative body weight must be considered even for 'non-obese' control groups used in insulin binding studies of various clinical conditions.

[Selective venous catheterization in the evaluation of androgenism]. / Selektive Venenkatheterisierung zur Abklärung von Androgenisierungserscheinungen.

In cases of rapidly increasing androgenism, virilism and androgenetic cycle disturbances it is essential to exclude the presence of an androgen-producing tumour. Serum levels of testosterone above 1.5 ng/ml and dehydroepiandrosterone sulphate values above 6700 ng/ml are suggestive of tumour. Functional tests, laparoscopy and imaging modalities are often less efficient. Selective vein catheterisation enables the diagnosis and localisation of such hormone-producing neoplasms (Kirschner and Jacobs, 1971). This paper presents the case report of the diagnosis of a Leyding cell tumour of the right ovary by means of selective vein catheterisation. The tumour was not palpable and had not been detected on laparoscopy. The procedure is extensively described and discussed.

[Androgenetic amenorrhea]. / Die androgenetische Amenorrhoe.

Virilism in females is often associated with menstrual disorders. There is an evident correlation between the severity of virilism, the level of androgens and the degree of menstrual disorder. A study was carried out between January 1978 and December 1980 on 75 women with various degrees of virilism. The majority of women with severe hirsutism and male-type alopecia were found in the group with amenorrhoea. Furthermore, the four cases with the full-blown picture of severe virilism were found exclusively in this group. Clarification of the virilizing manifestations on the basis of a determination of the basic hormonal status (including the steroid fractions), the dexamethasone suppression test (including the HCG stimulation test) and the oestrogen-gestagen suppression test, diagnostic laparoscopy and phlebography of the adrenal gland is discussed and the methods evaluated.

[The pulsatile administration of releasing hormone (GnRH) for the treatment of hypothalamic amenorrhea]. / Die pulsatile Releasinghormon-(GnRh-)Gabe zur Behandlung der hypothalamischen Amenorrhö.

12 women with hypothalamic amenorrhoea (degrees II to IIIb) were given pulsatile releasing hormone in 14 treatment cycles. The minipump "Zyklomat" (Ferring Ges.m.b.H., Kiel) with a treatment set giving 0.8 mg LH-RH was used in all cases. In 86% (12 out of 14) of the treated cycles ovulation was recorded. 3 out of 8 women who desired a baby became pregnant. 1 of these pregnancies followed directly on a treatment cycle whilst the other 2 pregnancies resulted from spontaneous biphasic cycles following the treatment cycle. In 4 women pulsatile releasing hormone was used to examine the functional reaction of the pituitary gland and the ovary. In this group 1 spontaneous biphasic cycle was seen following the induced ovulatory cycle.

[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism]. / Die Hormonersatztherapie mit einem perkutan wirksamen Oestradiol-Gel und oral verabreichtem mikronisierten Progesteron. Auswirkung auf klimakterische Symptome und den Lipidstoffwechsel.

In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.

Rare manifestations of the ovarian hyperstimulation syndrome: a report of two cases.

The increasing practice of ovulation induction has made ovarian hyperstimulation syndrome (OHSS) a frequent clinical problem which can also become life-threatening. Two unusual cases of OHSS are described. The first patient presented with a unilateral pleural effusion. The second patient developed severe OHSS after a low-dose protocol with highly purified follicle stimulating hormone (FSH HP) and in the absence of risk factors.

Pregnancies in patients with premature ovarian failure.

We present 5 women with premature ovarian failure (POF) who were treated with different regimes and conceived. Three patients conceived spontaneously while on cyclic estrogen/progestagen replacement therapy. One patient conceived after high-dose gonadotrophin treatment. Embryo transfer with oocytes donated from a third party donor was performed in one patient abroad. Due to legal reasons the heterogeneous oocyte donation for patients with POF cannot be performed in some countries such as Austria. Therefore, many patients who desire pregnancy cannot receive optimal treatment for their condition.

[Hormonal replacement therapy in patients with cervical and ovarian cancers]. / Hormonsubstitution bei Zervixkarzinom und Ovarialkarzinom.

Hormonal replacement therapy in women following primary treatment for squamous cell carcinoma of the cervix uteri is harmless. In case of adenocarcinoma of the cervix, guidelines for hormonal replacement therapy according to those valid for endometrial cancer are recommended. In women treated for ovarian cancer, a combined cyclic or continuous estrogen/gestagen substitution - the latter also in hysterectomized women - is to be favored. Signs of androgen deficiency are to be respected. Short-term clinical, sonographical, and biochemical control investigations are recommended.

[Pathogenesis and diagnosis of polycystic ovary syndrome]. / Pathogenese und Diagnostik des polyzystischen Ovarsyndroms.

OBJECTIVE: Growth factors (human growth hormone, HGH; insulin-like growth factor I, IGF-I) and insulin were evaluated concerning their pathogenetic significance in patients with polycystic ovary syndrome (PCOS). METHODS: Twenty-eight women with signs of PCOS were examined; 24 women without signs of PCOS served as controls. RESULTS: Women with PCOS showed significantly increased androgen, IGF-I, insulin and glucose levels, higher glucose concentrations in the oral glucose tolerance test and a higher body mass index. The concentration of HGH, the HGH/IGF-I ratio and the number of insulin receptors on red blood cells were significantly decreased in women with PCOS. The insulin receptor affinity, the maximum binding and the insulin-receptor complex were increased in PCOS patients. CONCLUSION: A decreased number of insulin receptors, a disturbed insulin receptor binding, the resulting hyperinsulinemia as well as high levels of IGF-I are to be considered as important factors in the pathogenesis of PCOS.

Polycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.

Thirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH production. We discuss the possible mechanisms causing elevation of plasma Sm-C, HGH, steroid hormones, excessive food intake, and possibly prolactin seem responsible for the clinical manifestation of increased Sm-C production in adolescence and for its level in the fertile years of patients.

[Criteria of the maturity of follicle and oocyte within the scope of in vitro fertilization. An overview]. / Reifekriterien von Follikel und Eizelle im Rahmen der In-vitro-Fertilisierung. Eine Ubersicht.

The duration of preincubation of aspirated oocytes is essential for successful in vitro fertilization. The duration has to be varied according to the maturity of the oocyte and the follicle. The maturity of the oocyte corona-cumulus complex is assessed primarily by light microscopy. Additional information is provided by measurements of steroids, pituitary hormones, and proteins (such as inhibin, alpha 1-Antitrypsin, fibrinogen, plasminogen activator, collagenolytic enzymes, alpha 2-macroglobulin, fibronectin, glycosaminoglycans, insulin, insulin-like-growth-factors) in the follicular fluid. Complex measurements of so-called regulators of oocyte maturation (cAMP, oocyte maturation inhibitor, prostaglandins) is of high academic interest. Cytologic parameters, the chemotactic activity of the granulosa cells and serial ultrasound studies are of practical importance for evaluating the maturity of the growing follicle.

[Significance of thyroid function in the treatment of sterility]. / Die Bedeutung der Schilddrüsenfunktion im Rahmen der Sterilitätsbehandlung.

Latent subclinical hypothyroidism represents a particular problem in treatment for sterility, and can only be diagnosed after the results of a TRH test have been obtained (delta TSH > 15 microE/ml). Bearing these results in mind and by the administration of thyroid gland hormones or combinations of gonadotropins or clomifen, pregnancy rates in women with anovulatory sterility can be improved.

[Sterility in hyperprolactinemic amenorrhea]. / Sterilität bei hyperprolaktinämischer Amenorrhoe.

Infertility caused by hyperprolactinemic amenorrhea may be complicated by pituitary adenoma. In a group of 36 women with amenorrhoea-hyperprolactinemia-syndrome were 15 infertility-patients. 10 of them had prolactin levels above 100 ng/ml. In 6 patients a prolactinoma was removed microsurgically. In every case further treatment was necessary to get normal cycles. 8 of these 10 infertility-patients became pregnant.