Sperm survival studies in peritoneal fluid from infertile women with endometriosis and unexplained infertility.

Peritoneal fluid (PF) volume and sperm survival (motility and velocity) were studied in PF from women with unexplained infertility, infertile women with endometriosis and fertile women without endometriosis using a laser light scattering technique. PF volume was significantly larger in the group of women with unexplained infertility (P less than 0.025) and in infertile women with endometriosis (P less than 0.003) when compared with fertile women. There was a significant reduction in the percentage motile sperm in women with unexplained infertility (P less than 0.001) and in infertile women with endometriosis when compared with fertile women (P less than 0.001). In infertile women with endometriosis a positive correlation was observed between peritoneal fluid volume and reduction in the percentage of motile sperms (P less than 0.01).

Role of copper in IUDs.

PIP: This report analyzes the contraceptive potential of copper IUDs. The antifertility action of copper in IUDs is considered to involve 1) inhibition of zinc-containing metalloenzymes in the uterus, 2) reduced activity in the endometrial steroid receptor, 3) production of low levels of human chorionic gonadotropin in the luteal phase, 4) depression of ovum transport through the uterine tubes and inhibition of the penetration of cervical mucus by sperm, 5) elevation of the fibrinoloytic activity of the endometrium, and 6) depression of the synthesis of prostaglandins. These biochemical and physiological changes in response to copper released from the IUD are thought to cause only a local effect and systemic accumulation of copper from the device is considered unlikely. The rate of release of copper varies during the time the device remains in the uterus, declining exponentially during the 1st 2 years of use and then increasing as a result of destabilization and fragmentation of the accumulated layer of copper corrosion products. Accelerated copper loss is associated with menorrhagis, higher parity, and the presence of a cervical lesion at the time of IUD insertion. However, accelerated loss of the copper coil does not seem to cause either copper toxicity or decreased contraceptive efficiency. Women with insulin-dependent diabetes may manifest a different copper corrosion process and possibly a higher incidence of contraceptive failure. Since copper IUDs must be replaced more often than inert devices, there is a risk of increased incidence of pelvic inflammatory disease, reported to occur more frequently after replacement of an IUD. The longterm retention of copper IUDs probably has the same risk of infection as that associated with inert devices, and there is no evidence to link the presence of copper with any bacteriostatic or bactericidal action in vivo. The probability of fragmentation is reduced by new types of devices in which the copper wire is replaced by copper bands or a core of an inert metal is included inside the copper wire. It is concluded that copper IUDs, especially the newer devices with a more stable copper component, provide a successful fertility control method.^ieng

Degradation of the copper-releasing intrauterine contraceptive device and its significance.

Measurements were made of the copper remaining on used Gravigard intrauterine contraceptive devices (IUCDs) that had been in utero for up to 40 months. The topography and composition of the surface deposits were analysed by scanning electron microscopy and energy-dispersive X-ray analysis. The rate of copper loss decreased exponentially from 0.42 mumol d-1 (26.7 micrograms d-1) upon insertion to 0.056 mumol d-1 (3.6 micrograms d-1) after 26 months of use; between 27 and 40 months of use a linear release of 0.32 mumol d-1 (20.3 micrograms d-1) was observed. There was no correlation between this changing rate of copper loss and the pregnancy rate with the device in situ. The changes in the rate of copper loss were probably due to the growth of a surface corrosion product which, due to internal stresses, fractured after about 2 years and exposed fresh copper; this results in a progressive increase in breakage of the copper wire after 3 years. It is recommended that a copper IUCD of this type be replaced after 3 years.

PIP: Measurements were made of the copper remaining on used Gravigard IUDs that had been in utero for up to 40 months. The topography and composition of the surface deposits were analyzed by scanning electron microscopy and energy-dispersive x-ray analysis. The rate of copper loss decreased exponentially from 0.42 mcmol d-1 (26.7 mcg d-1) upon insertion to 0.056 mcmol d-1 (3.6 mcg dz-1) after 26 months of use; between 27-40 months of use, a linear release of 0.32 mcmol d-1 (20.3 mcg dz-1) was observed. There was no correlation between this changing rate of copper loss and the pregnancy rate with the device in situ. The changes in the rate of copper loss were probably due to the growth of a surface corrosion product which, due to internal stresses, fractured after about 2 years and exposed fresh copper; this results in a progressive increase in copper wire breakage after 3 years. It is recommended that a copper IUD of this type be replaced after 3 years.

Terminal glycosylation in human cervical mucin.

L-Fucose and N-acetylneuraminic (sialic) acid occupy terminal positions on the oligosaccharide side-chains of human cervical mucin but the addition of both these monosaccharides to the same carbohydrate acceptor residue is kinetically unfavourable. The following evidence suggests that the levels of L-fucose are more sensitive to regulation than those of N-acetylneuraminic acid: (1) tissue levels of sialyltransferase (EC 2.4.99.1) activity are 20-30 times greater than those of fucosyltransferase (EC 2.4.1.68); (2) both glycosyltransferases are susceptible to inhibition by their nucleotide products but a comparison of the Ki and the apparent Km of these enzymes shows that modulation of fucosyltransferase is more probable; (3) Postsecretory removal of L-fucose from cervical mucin is probably due to the high levels of mucus-associated alpha-L-fucosidase. Furthermore the activity of this enzyme is probably modulated by the pH gradient within the cervix. Mucin glycosylation can be visualized by autoradiography using [3H]L-fucose applied to cervical explants in organ culture. Mucus production during this process is not sensitive to exogenous ovarian steroid hormones, though in other aspects the secretory process appears normal. It is proposed that the cyclicity of mucus rheology is not directly influenced by an action of these hormones on mucin synthesis or hydration.

Inhibition of human and bovine sperm acrosin by divalent metal ions. Possible role of zinc as a regulator of acrosin activity.

Human and bovine spermatozoa have been collected and washed repeatedly with isotonic saline to remove seminal plasma inhibitors and activate the acrosin. Then the acrosin activity of the cells was assayed with alpha-N-Benzoyl-DL-Arg-beta-naphthylamide (BANA). It was found that the surface-bound enzyme was not inhibited by high molecular weight inhibitors of trypsin but was markedly inhibited by low molecular weight trypsin inhibitors. Divalent metals (Zn++, Cu++, Hg++, Co++, Cd++) were all efficient inhibitors of acrosin on the washed cells. It was shown that the removal of zinc or copper from acrosin completely restored activity. It is proposed that the different levels of zinc in the male and female genital tract regulate acrosin activity. Aged cells released a soluble acrosin which was inhibited by serum and seminal plasma inhibitors of trypsin-like enzymes as well as by zinc ions in an identical manner to the surface-bound enzyme.

Glycosyltransferases of the human cervical epithelium. I. Characterization of a beta-galactoside alpha-2-L-fucosyltransferase and the identification of a beta-N-acetylglucosaminide alpha-3-L-fucosyltransferase.

Using phenyl beta-D-galactoside as an acceptor, alpha-2-L-fucosyltransferase activity was identified in human cervical epithelium with pH optima at 6.0 and 7.2. The different response to p-chloromercuribenzoate, and ability to utilise asialofetuin as an acceptor, suggests the presence of two fucosyltransferases. The acid form is probably involved in glycoprotein synthesis in vivo. At pH 6.0, fucosyltransferase has a temperature optimum of 25 degrees C, requires the presence of Triton X-100 and either manganese or magnesium for maximal activity, and has Km values for GDP-L-[14-C]fucose and phenyl beta-D-galactoside of 32.1 . 10(-6) M and 8.2 . 10(-3) M, respectively. Guanosine nucleotides are potent inhibitors of the fucosyltransferase reaction; GDP is a competitive inhibitor while, depending on its concentration, GTP can either inhibit or activate the reaction. The alpha-L-fucosidase present in cervical tissue has negligible activity towards the enzyme product, phenyl-alpha-2-L-[14C]fucosyl-beta-D-galactoside. The use of high and low molecular weight acceptors indicates the presence of a beta-N-acetylglucosaminide alpha-3-L-fucosyltransferase and an N-acetylgalactosaminide fucosyltransferase.

Glycosyltransferases of the human cervical epithelium. II. Characterization of a CMP-N-acetylneuraminate: galactosyl-glycoprotein sialyltransferase.

GMP-N-Acetylneuraminate: galactosyl-glycoprotein sialytransferase (CMP-N-acetylneuraminate: D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) activity was identified in the human cervical epithelium. The enzyme has a pH optimum of 6.0, a temperature optimum of 28 degrees C, and demonstrates a partial requirement for Triton X-100. Michaelis constants for asialofetuin and CMP-N-acetyl[14C]neuraminic acid are 0.64 . 10(-5) M (expressed as the concentration of terminal galactose residues) and 2.05 . 10(-5) M, respectively. Sialytransferase demonstrated minimal affinity for the low molecular weight acceptors tested, and may have a requirement for a glycoprotein acceptor having a terminal N-acetyllactosamine (Gal beta (1 leads to 4)GlcNAc) type structure. Cytidine nucleotides are potent inhibitors of the sialyltransferase reaction; CMP acts as a competitive inhibitor.

Carbonic anhydrase activity in human cervical mucus and its response to various contraceptives regimes.

Carbonic anhydrase activity is present in human cervical mucus throughout the normal menstrual cycle. Lowest activity occurs in the ovulatory phase. A similar pattern of activity is seen in the presence of either an 'inert' or copper-releasing intrauterine contraceptive device (IUCD). The overall levels of activity are not significantly altered by the presence of either type of IUCD. A cyclic pattern of activity is retained even though endogenous ovarian function is suppressed by combined oestrogen-progestogen oral contraceptives.

PIP: Carbonic anhydrase activity and its response to various contraceptive regimes were studied in human cervical mucus. Carbonic anhydrase activity was found to be present throughout the normal menstrual cycle. The lowest activity occurred at the time of ovulation (p .01). A similar pattern of activity was seen in the presence of either an "inert" or copper-releasing IUD. The overall levels of activity were not markedly altered by the presence of either type of IUD. A cyclic pattern of activity was retained even though endogenous ovarian function was suppressed by combined estrogen-progestogen oral contraceptives.

The scanning electronmicroscopy of human cervical mucus in the non-pregnant and pregnant states.

The ultrastructure of the high viscosity phase of human cervical mucus was studied by scanning electronmicroscopy. In the normal woman, sequential mucus samples taken throughout the menstrual cycle showed a honeycomb-like structure with interconnecting channels separated by thin membraneous walls. The diameter of the channels in the mucus was 2 to 6 mum in the early follicular phase, 30 to 35 mum in the late follicular phase and 4 to 6 mum in the luteal phase. During the first trimester of pregnancy and also at the beginning and end of the menstrual cycle a compact, dense form of mucus structure was observed. In women using either copper-releasing or pharmacologically inert intrauterine contraceptive devices (IUCDs), the basic structure was similar to that seen in normal women. The channel diameters were normal in women using the inert IUCD but the mucus from women using a copper-releasing IUCD showed a slight decrease in the late follicular phase channel diameter which was dependent on the time the device had been in place. Globular appendages to the membraneous walls of the mucus were observed in the presence of a copper-releasing IUCD.