Pregnancy: Pregnancy and implantation rates in normal replacement versus stimulated cycles

The relative importance that endometrial development and embryoquality have on implantation rates achieved with assisted reproductivetechnology (ART) is the subject of controversy. Ovarian stimulationhas been repeatedly mentioned as having a detrimental effecton endometrial receptivity (Paulson et al., 1990, Fertil. Steril.,53, 870–874). We compared pregnancy and implantation ratesachieved with ART during stimulated cycles and hormonal replacementcycles, in patients matched for the following criteria: age<35 years for the patient donating oocytes; transfer of atleast two good quality embryos/oocytes and good quality transfer.All transfer cases performed during hormonal replacement cycleswere done with donated oocytes. Comparison of results betweentechniques was not attempted due to potential differences inpopulations. The pregnancy and implantation rates achieved witheach technique during stimulated and hormonal replacement cycleswere not statistically different. In contradiction to previousresults, our data suggest that differences in uterine receptivitybetween stimulated and hormonal replacement cycles in the agegroup studied are not of critical importance in embryo implantation.Good embryo quality appears to be the dominant factor in determiningthe success of ART.     

Pituitary responsiveness to LH-RH during gestation and puerperium in the rhesus monkey

Pituitary gonadotropin response to luteinizing hormone-releasing hormone (LH-RH; 150 micrograms, administered intravenously) was studied during pregnancy and the early postpartum period in rhesus monkeys. Challenge tests were performed approximately every three weeks during pregnancy and every two weeks after delivery, in breast-feeding and non breast-feeding animals. It was found that the response to the releasing factor was completely abolished as early as day 20 after conception. This absence of pituitary responsiveness to LH-RH continued throughout pregnancy. The return of the response during the puerperium occurred as early as day 15 post-delivery in non-breast-feeding monkeys, but remained abolished up of the response to LH-RH in FSH and LH concentration was observed, in that LH levels increased 70%-90%, whereas FSH levels increased only 20%-30%. Serum prolactin (PRL) levels in breast-feeding animals presented a slight increase the first week post-delivery and thereafter, and decreased gradually until they reached normal levels four weeks post-delivery. In contrast, concentrations of serum PRL in non-breast-feeding animals decreased abruptly to normal levels within the first week post-delivery. These results demonstrate that, due to its similarity to the human, the rhesus monkey is an excellent animal model in which to study pituitary function during pregnancy and the puerperium.     

Leptomeningeal tumor in primarchy central nervous system lymphoma: Recognition,significance, and implications

The true incidence of leptomeningeal tumor in priMarchy central nervous system lymphoma is unknown. We studied prospectively the cerebrospinal fluid profile of 96 patients without acquired immunodeficiency syndrome but with priMarchy central nervous system lymphoma at diagnosis, at completion of treatment, and at recurrence. Magnetic resonance images and pathology slides were examined for evidence of leptomeningeal tumor. Leptomeningeal tumor was diagnosed by (1) positive findings on cerebrospinal fluid cytology, (2) leptomeningeal or subependymal enhancement on magnetic resonance imaging, or (3) pathological evidence of leptomeningeal tumor. We recorded whether treatment directed against the leptomeninges was given. Cerebrospinal fluid was examined in 86 of 96 patients at diagnosis and 29 of 42 at recurrence. The incidence of leptomeningeal tumor was 42% at diagnosis and 41% at recurrence. Only elevated levels of protein and lactate dehydrogenase isoenzyme-5 were significantly associated with leptomeningeal tumor (r = 0.012, p = 0.016, respectively). Treatment against the leptomeninges was significantly associated with the probability of achieving a complete response and a longer freedom from relapse. Patients older than 50 years had a worse disease-specific survival but a similar probability of responding to therapy as younger patients. Our data show that leptomeningeal tumor in priMarchy central nervous system lymphoma is more prevalent than originally thought, and indicate the need for therapy inclusive of the leptomeninges in all patients.     

Germ cell tumors of the CNS in children: recent advances in therapy

Primary germ cell tumors of the central nervous system are rare neoplasms, accounting for no more than 2% of all malignancies in children and young people under 20 in the Western hemisphere. They have unique features related to age at diagnosis and sites of origin, as well as race and gender predilection. Prognosis has been clearly shown to be strongly related to pathological classification as either pure germinoma or nongerminomatous germ cell tumor, although many of these lesions are comprised of mixed elements. The presence of serum or cerebrospinal fluid tumor marker elevation has been an essential determinant of response to treatment. Because of the deleterious effects of irradiation on the immature nervous system, investigators have used chemotherapeutic strategies that either reduce or eliminate radiation therapy. In this article, we review the most recent advances in therapy for CNS germ cell tumors in the pediatric population and highlight the importance of cooperative trials in this setting. Received: 12 April 1999     

Rare association of ovarian implantation site for patients with heterotopic and with primary ectopic pregnancies after ICSI and blastocyst transfer

Two cases of patients with ruptured ovarian pregnancies (P1 = ovarian heterotopic and P2 = primary ovarian ectopic) after intracytoplasmic sperm injection and blastocyst transfer are presented. Laparoscopy was performed on day 40 and day 27 after transfer in cases P1 and P2 respectively. In both cases the ectopic pregnancies were located on the left ovary and were successfully removed by laparoscopy preserving the ovaries. In case P1 the intrauterine pregnancy was not affected. A healthy boy was born after 37 weeks of pregnancy. In this way, potential fertility of the patients and the intrauterine pregnancy were maintained. These cases occurred during a series of blastocyst transfers in which 129 pregnancies were obtained. There were no cases of ovarian ectopic/heterotopic pregnancies from January 1996 to September 1999 in 814 pregnancies obtained from day 2 or day 3 embryo transfers. Because the ovarian ectopic pregnancies occurred in patients with day 5 embryo transfer who otherwise did not have any predisposing factors for ectopic pregnancy, it is advisable to conduct a large scale analysis of future data about the possible association between blastocyst-stage embryo transfer and the somewhat higher risk of unexpected complications of clinical outcome.     

Changes in expression of adenyl cyclase activity in human endometrium during hormone replacement therapy and ovarian stimulation.

We have investigated membrane fractions prepared from human endometrium for activity of the signalling adenyl cyclase (AC). We characterized the AC guanine nucleotide-binding proteins (G proteins) and examined the changes in AC activity during evaluation cycles of oestrogen and progesterone replacement therapy as well during ovarian stimulation cycles. AC activity was determined by the conversion of substrate ATP into cyclic AMP under basal conditions and in the presence of guanine nucleotide or forskolin. G proteins were determined by Western Blot using specific polyclonal antibodies against Gsalpha, Gi1,2alpha and Gi3alpha. Our results indicate that endometrial AC was highly responsive to activation by both guanine nucleotide and forskolin and its rate of cyclic AMP production was highly pronounced. Mean activity reached 920 pmol/l/min/mg membrane protein in the presence of forskolin, a value approximately 5-fold higher than those detected in corpus luteum. Hormonal induction of AC activities increased Gsalpha protein, which couples with and stimulates the catalytic component of AC. We conclude that human endometrium is rich in AC and that enzyme activity is induced by oestrogen and progesterone treatment. These data strongly support the concept that the transmembrane signalling AC system and its messenger cyclic AMP are major regulators of endometrial function in the human.     

Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii

It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1(19) combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1(19) and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1(19) were elevated compared to the MSP1(19) alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1(19) response was observed. Boosting of anti-MSP1(19) did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.     

Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.     

Developmental competence of mouse embryos following zona drilling using a non-contact holmium: yttrium scandian gallium garnet (Ho: YSGG) laser system

The purpose of this study was to assess the efficacy of theholmium: yttrium scandian gallium garnet (Ho:YSGG) laser, operatingin a pipette-free, non-contact mode, to assist hatching andsustain normal embryonic development. Two-cell mouse embryoswere recovered and assigned to laser-assisted hatching (LAH)treatment or control human tubal fluid (HTF) culture with orwithout serum (HTF-s, HTF-o) or with late serum supplementation(HTF-o/s). The basic experimental apparatus for LAH consistedof a stationary 2.1 µm Ho: YSGG laser beam directed througha mechanical shutter into an input port of a Zeiss Axiomat invertedmicroscope. Fewer (P < 0.05) embryos developed to the blastocyststage in the HTF-s group (81%) than in the LAH (90%), HTF-o(94%) and HTF-o/s (92%) groups. The level of hatching was significantlyincreased (P < 0.01) after the LAH treatment (57%) comparedto HTF-o/s (32%), HTF-s (18%) or HTF-o (5%). Implantation rateswere not significantly impaired following the LAH treatment(21%). These data demonstrate that LAH using the Ho: YSGG laseris a simple, accurate and effective procedure for assisted hatching.     

Prolactin and gonadotrophin dynamics in response to antagonists of LHRH and dopamine in ovariectornized rhesus monkeys: a dissection of their common secretion

This experiment was designed to study the prolactin (PRL) andgonadotrophin response to an inhibitory analogue of luteinizinghormone releasing hormone (LHRH-A; ORG 30276) and a dopamineantagonist, metoclopramide (MCP), in castrated female rhesusmonkeys. The LHRH-A given as an i.v. bolus followed by an Infusion2 h later induced a significant decline in circulating PRL levelsreaching a maximum suppression 1 h after initiation of the LHRH-Ainfusion. Intravenous administration of MCP, performed 1 h afterbegining the LHRH-A infusion, resulted in a prompt and abruptrise in PRL levels in the LHRH-A group as well as in the controls.Luteinizing hormone (LH) and follicle stimulating hormone (FSH)levels showed a progressive decline during LHRH-A treatment.Injection of MCP did not affect the levels of LH and FSH ineither of the groups. The data obtained demonstrate in primatesthat the prolactin inhibitory effect of LHRH-A is easily overcomeby the dopamine antagonist, MCP, whereas the LHRH-A-inducedgonadotrophin suppression remains unaffected by MCP.