Aarne Koskimies

Distribution of placental protein 14 in tissues and body fluids during pregnancy

Summary. Placental protein 14 (PP14) levels were measured in serum samples from non‐pregnant and pregnant women. amniotic fluid, cord blood, and extracts of placenta, decidua and fetal membranes. The levels were low (15–40 μg/l) in serum of non‐pregnant women. In four pregnancies following in‐vitro fertilization, the serum PP14 levels started to rise 2–12 days after embryo replacement. In normal pregnancy, the highest serum PP14 concentrations (up to 2200 μg/l) were detected between 6 and 12 weeks. After 16 weeks the level decreased and plateaued at 24 weeks to around 200 μg/l. In amniotic fluid, the highest PP14 levels (232 mg/l) were found between 12 and 20 weeks, being considerably higher than those in maternal serum throughout pregnancy. In cord blood, the levels were low (15–22 μg/l) or undetectable. In early pregnancy decidua. the PP14 content was higher (41–160 mg/g total protein) than in late pregnancy decidua (60–2700 μg/g total protein). In amnion and chorion laeve, the PP14 concentration varied from 50 to 750 and 50 to 1000 μg/g protein, respectively. Early pregnancy placenta contained 0‐25‐15 mg/g and late pregnancy placenta 3–430 μg/g protein of PP14. These results show that the levels of PP14 in pregnancy serum have a similar profile to hCG, but in contrast to other placental proteins, the amniotic fluid PP14 levels are remarkably high. This may be explained by suggesting that decidua is a source of PP14.

Monitoring the LH Surge by Ultrarapid and Highly Sensitive Immunofluorometric Assay

A novel time-resolved immunofluorometric method is described for the estimation of human luteinizing hormone (LH) in serum and urine. The method utilizes two monoclonal antibodies: one reacting with the beta-subunit is adsorbed to the wall of a microtiter well, and the other is labeled with a fluorescent europium chelate and reacts with the alpha-subunit. The method is ultrarapid (15-30 min) and highly sensitive (1 IU/L). A large linear measuring range allows measurement of LH levels from 1 to 250 IU/L. For the monitoring of urinary LH, IFMA gives the same information as the Hi-Gonavis assay, but it has the advantages of greater sensitivity and a shorter assay time. For the determination of serum LH levels, an acceptable correlation was observed between radioimmunoassay and IFMA. Furthermore, IFMA has a greater sensitivity, and is more rapid and not dependent on the handling of radioactive materials.

Modifying effects of epidural analgesia or general anesthesia on the stress hormone response to laparoscopy for in vitro fertilization.

Modifying effects of epidural analgesia and general anesthesia on stress hormone release was studied during laparoscopy for in vitro fertilization (IVF). In 24 women follicle development was stimulated by clomiphene and gonadotropin treatment, and oocytes were collected by laparoscopy under epidural analgesia in 11 women and under fentanyl-supplemented nitrous oxide-oxygen anesthesia in 13. The plasma levels of immunoreactive β-endorphin (ir β-E), cortisol, and prolactin (PRL) did not change under epidural analgesia per se, but after the start of laparoscopy, increased release of all these stress hormones was observed. General anesthesia per se increased the release of PRL, whereas the release of cortisol and ir β-E decreased, probably due to the effects of fentanyl and thiopentone. During the stress attributed to laparoscopy, significantly more ir β-E and cortisol was released under epidural than under general anesthesia, whereas the release of PRL was more significant under general anesthesia. These results show that neither mode of anesthesia prevented the stress response to laparoscopy. In the subsequent midluteal phase, the mean plasma level of progesterone and the mean progesterone-estradiol ratio were significantly greater in the epidural than in the general anesthesia group, suggesting that the mode of anesthesia may have an effect on the luteal phase. The significance of this difference on the conception rate remained unsolved, however.

Infertility in women participating in a screening program for cervical cancer in helsinki

The purpose of the present study was to establish the occurrence of infertility in Finnish women aged 30, 35 and 40 years. The study is based on an interview by questionnaire carried out on women participating in screening for cancer by Pap smear. The participation rate is generally about 60%. A total of 4879 women were interviewed between May 1981 and April 1982. 149 incomplete replies were discarded and an additional 528 women not at risk of conception were excluded. The final analysis included 4202 women. Actual infertility, i.e., failure to establish pregnancy at the time of interview, occurred in 438 women (10.4%). The overall infertility rate was 15.4%. The primary infertility rate (5%) seems to be similar in all the age groups interviewed. Secondary infertility increased among women aged 30–40 years, from 4.1 to 9.9%. Actual infertility increased highly significantly between the age groups 30 and 40 years. A limited number of women are permanently infertile, but the percentage of those who at some point in their lives are involuntarily childless is higher.

A short luteal phase in cycles stimulated with clomiphene and human menopausal gonadotropin for in vitro fertilization

Of 70 cycles stimulated with clomiphene and human menopausal gonadotropin (hMG) for an in vitro fertilization-embryo transfer (IVF-ET) program, a short luteal phase of 11 days or less was found in 18. In this group the mean estradiol and progesterone levels were elevated in the early luteal phase. Despite the elevated initial values, progesterone levels fell rapidly at the mid luteal phase as a sign of premature luteolysis. The mean total amount of gonadotropin administered and the mean number of follicles punctured and of oocytes recovered did not show any significant difference between the groups of normal and short luteal phases. The present findings support the theory that hyperestrogenism in the early luteal phase may initiate the premature luteolysis observed in clomiphene-menopausal gonadotropin-stimulated cycles.

In vitro recovery of human chorionic gonadotropin-stimulated cyclic adenosine 3′,5′-monophosphate production in desensitized human granulosa-luteal cells*

Human granulosa-luteal cell production of cyclic adenosine 3,5-monophosphate (cAMP) and progesterone (P) were studied in response to purified human chorionic gonadotropin (hCG) in cultured cells from hyperstimulated follicles of in vitro fertilized patients. The hCG injection given to the patients 36 hours before laparoscopy caused partial desensitization of adenylate cyclase of these cells to gonadotropins. Preincubation of the cells in hormone free medium for 2 to 3 days significantly increased their cAMP responsiveness to hCG. P production was stimulated initially by hCG and showed no desensitization. In the cells preincubated for 72 hours without hCG, a subsequent stimulus of 50 ng/ml of hCG elicited maximal cAMP response, whereas 1 ng/ml of hCG was sufficient to bring about maximal P secretion. Time-course studies indicated that maximal cAMP response to hCG was obtained in 1 to 3 hours. Both basal and hCG-stimulated P accumulation continued to rise for up to 24 hours. Preincubation of granulosa-luteal cells from hyperstimulated follicles improves the cells cAMP responsiveness to hCG, whereas P response remains unaltered.