Transrectal electroejaculation combined with in-vitro fertilization: effective treatment of anejaculatory infertility due to spinal cord injury.

Infertility due to spinal cord injury (SCI) in young men is a frequent complication of their injury. When the simpler methods of management of the erectile and ejaculatory dysfunction that invariably follow the more severe types of SCI are not effective, then semen production by transrectal electroejaculation (TREE) combined with in-vitro fertilization (IVF) and embryo transfer is effective. A retrospective analysis is presented of data on the treatment and outcome of 35 couples who wished to have a family but in whom the male partner had suffered SCI. These 35 couples had 71 attempts at IVF with spermatozoa obtained following TREE. Normal fertilization and cleavage of the embryos occurred in 48.2% of the oocytes. Fresh embryos were transferred in 54 cycles and frozen-thawed embryos in 14 cycles. In all, 18 clinical pregnancies were achieved in 54 fresh and 14 frozen embryo transfer cycles, with a live birth rate of 16.5% (14/85) per treatment cycle started, 20.6% (14/68) per transfer cycle and 40.0% (14/35) per couple who started treatment, in a mean of 1.9 transfer cycles. We conclude that TREE combined with IVF and embryo transfer is an effective treatment for the infertility problems associated with SCI.

The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception.

The objective of this long-running study was to determine whether the addition of low-dose aspirin to a standard hormone replacement therapy (HRT) protocol improved uterine perfusion during assisted conception. A total of 99 women scheduled for frozen embryo replacement were studied. Endometrial preparation was with a standard buserelin/HRT protocol. Uterine perfusion was assessed by Doppler ultrasound and classified as impaired or normal. In their first attempts, those with impaired perfusion (group I, n = 37) received low doses of aspirin [150 mg (n = 26) or 300 mg daily (n = 11)], starting from day 13 of HRT. Women with normal perfusion (group II) did not receive aspirin. In subsequent attempts, those from group I were arbitrarily allocated to start aspirin on day 1 or day 13 of HRT, and 10 women from group II were arbitrarily selected to receive aspirin from day 1 of HRT. In group I, the cancellation (46 versus 36%) and pregnancy rates (15 versus 25%) in those who received 150 or 300 mg aspirin daily were similar. In those with cancelled first attempts, good perfusion was achieved in 82 versus 20% (P < 0.02) of subsequent attempts using aspirin from day 1 versus day 13 of HRT. Higher pregnancy rates (47 versus 17%) were achieved in those taking aspirin from day 1 of HRT. In group II, pregnancy rates were not statistically different in those who did or did not receive aspirin during their subsequent attempts (10 versus 35%). The addition of low-dose aspirin to a standard HRT protocol in women with impaired uterine perfusion is associated with improved blood flow and satisfactory pregnancy rates.

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos.

The objective of this retrospective study was to compare the birth characteristics and perinatal mortality of babies conceived from the use of cryopreserved embryos with those resulting from in-vitro fertilization (IVF) and fresh embryo transfer. A total of 232 consecutive births, one pregnancy termination and a total of 283 babies in the cryopreserved group were studied. The IVF data included 763 births, three terminations and 961 babies, based on a previous analysis. There was no difference in the incidence of twin (18 versus 19%) and triplet births (2 versus 3%) in the cryopreserved and IVF groups respectively. The mean gestational age and birthweight of singleton, twin and triplet births were not significantly different between the groups. No difference was found in the perinatal mortality rates. The incidence of major congenital malformations in the cryopreserved group (1%) was significantly lower than that in the IVF group (3%; P < 0.05). It is concluded that the birth characteristics of babies conceived from cryopreserved/thawed embryos are similar to those from fresh embryos. There are fewer congenital malformations in the cryopreserved group.

Pronuclear, cleavage and blastocyst histories in the attempted preimplantation diagnosis of the human hydatidiform mole.

We report a study of fertilization, syngamy and embryonic development in 14 oocytes from a woman with four previous pregnancies involving complete hydatidiform moles. Serial observations of pronuclear movements and syngamy were compared to those in a group of 10 multipronucleate embryos from other patients. One embryo and possibly two others developed normally or near-normally. The others displayed immediate cleavage or had one or three pronuclei. The tripronucleate eggs displayed various anomalous forms of growth. The unipronucleate eggs passed through a double form of syngamy, which might have involved chromosome doubling, and could have developed as androgenetic diploids. We suggest a hypothesis to explain these unusual observations.

Replacement of frozen-thawed embryos in artificial and natural cycles: a prospective semi-randomized study.

This prospective partly-randomized study assessed the relative efficacy of two strategies of patient management for the replacement of frozen-thawed embryos. A luteinizing hormone-releasing hormone (LHRH) agonist was used to induce a temporary hypogonadism in a group of patients who were then prepared for implantation by endometrial priming with hormone replacement therapy (HRT): oral oestradiol valerate and then oestradiol valerate and injections of progesterone. A second group of patients had their frozen-thawed embryos replaced during their natural cycles. Of the 84 patients treated with the LHRH regimen, 80 had embryos replaced and 16 (20%) clinical pregnancies were established. Of the 78 patients treated with natural cycles, 70 had embryos replaced and 14 (20%) achieved clinical pregnancies. There were no statistical differences between the two groups in terms of age, obstetric history, duration of infertility, number of oocytes retrieved and fertilized or the number of embryos frozen following ovarian stimulation in the embryo 'generating' cycle. In terms of pregnancy rates, both protocols were equally effective. However, the LHRH-HRT protocol was of great value in the management of oligomenorrhoeic patients and in establishing standard conditions for implantation in cyclic patients.

Endocrine monitoring for assisted human conception.

The pregnancy potential of an assisted conception treatment cycle increases with the number of oocytes or embryos returned to the patient. It is therefore necessary for the patient to undergo a form of follicular stimulation which will result in the recruitment of a cohort of preovulatory follicles and hence supernumerary oocytes. The commonest superovulation regimen used consists of clomiphene citrate combined with human menopausal gonadotrophins. However the administration of these stimulants increases circulatory levels of LH and perturbs the normal feedback systems of the hypothalamus-pituitary-ovarian axis leading to an attenuation of the endogenous LH surge. The normal and synchronous development of the uterine endometrium may also be impaired which could lead to a failure of implantation. These inherent problems mean that rapid endocrine monitoring facilities are mandatory for optimizing the outcome of the cycle. Recent use of GnRH analogue agonists which effectively reduce tonic levels of LH and inhibit the surge have brought about a significant improvement in pregnancy outcome. However some endocrine monitoring is required even after pituitary desensitisation in order to reduce the incidence of the ovarian hyperstimulation syndrome.

Evidence for the involvement of dopamine and 5-hydroxytryptamine in the regulation of the preovulatory release of luteinizing hormone in the domestic hen.

Injections of the dopamine (DA) precursor L-dopa and the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan, beginning 6 hr before the predicted preovulatory release of LH, abolished the LH surge and blocked ovulation. The inhibitory effect of the drugs on the preovulatory release of LH was not reversed by injection of progesterone. This showed that the drugs inhibited LH release by acting on the central nervous system rather than peripherally, by inhibiting the release of progesterone from the ovary. The turnover rates of DA and 5-HT were estimated during the ovulatory cycle in the median eminence, the posterior hypothalamus, and the anterior hypothalamus. The turnover rates of the two monoamines were estimated from their rates of accumulation after inhibiting their catabolism with the monoamine oxidase inhibitor pargyline. Turnover of DA and 5-HT in the median eminence was depressed during the preovulatory release of LH and decrease in the anterior hypothalamus when preovulatory LH levels were increasing. Observations were also made of changes in the concentrations of hypothalamic DA, 5-HT, noradrenaline (NA), and adrenaline (A) during the ovulatory cycle. Concentrations of DA, 5-HT, and NA increased in the anterior hypothalamus and decreased in the posterior hypothalamus during the 4 hr before the peak of the preovulatory release of LH. These results strengthen the view that hypothalamic DA and 5-HT play a role in the regulation of the preovulatory release of LH by a reduction in inhibitory inputs on LHRH neurones.

Short-term luteinizing hormone-releasing hormone agonist treatment: prospective trial of a novel ovarian stimulation regimen for in vitro fertilization.

Over a period of 4 months, 262 infertile couples participated in a prospective pseudorandom trial of a novel short-term luteinizing hormone-releasing hormone/human menopausal gonadotropin (LH-RH/hMG) treatment; the short-Buserelin-gonadotropin (Hoechst, Hounslow, United Kingdom) regimen. Patients treated with the short-Buserelin-gonadotropin regimen had a significantly higher likelihood of achieving pregnancy than patients treated with the standard clomiphene citrate (CC)/hMG regimen (respectively, 35.5% and 18% per treatment cycle). A significantly higher number of eggs were collected after short-Buserelin-gonadotropin treatment than CC/hMG, but the proportion of patients having a given number of embryos replaced was similar in the two groups. The short-Buserelin-gonadotropin-treated patients were distinguished from the CC/hMG-treated group by significantly lower levels of LH in the late follicular phase and a lower plasma level of estradiol. A detrimental relationship between elevated endogenous LH secretion and failure of implantation has been established. The nature of the short-Buserelin-gonadotropin regimen provokes high levels of endogenous gonadotropin secretion in the early follicular phase and induces a suppression of gonadotropin secretion in the late follicular phase. This may be the physiologic basis of the greater implantation rate after short-Buserelin-gonadotropin treatment than is seen with conventional CC/hMG treatment.

The functional activity of hypothalamic dopamine in broody bantam hens.

An assessment was made of the possible role of hypothalamic dopamine in the regulation of changes in plasma prolactin and LH in laying and broody bantam hens. Specific dopamine-binding sites were identified, using [3H]domperidone, in the anterior pituitary gland and in the anterior and posterior hypothalamus. The mean concentrations of dopamine-binding sites in both parts of the hypothalamus were 59-66 fmol/mg protein and did not differ between laying and incubating hens. The concentration of dopamine binding sites in the anterior pituitary gland was significantly (P less than 0.001) greater in laying than in incubating hens (278 +/- 46 compared with 420 +/- 32 fmol/mg protein, n = 5). The turnover rates of dopamine were compared in the anterior and posterior hypothalami of laying, incubating and nest-deprived hens. The turnover rates were estimated from the rate of accumulation of dopamine after inhibiting its catabolism using the monoamine oxidase inhibitor, pargyline, or by measuring the ratio of the concentrations of dopamine and its major metabolite, homovanillic acid. Both methods gave the same results. The turnover of dopamine was increased in the anterior but not posterior hypothalamus of incubating hens when compared with laying or nest-deprived hens. These results show, for the first time in birds, that the anterior pituitary gland contains specific binding sites for dopamine and that the concentration of these binding sites is inversely related to the concentration of plasma prolactin. The marked increase in dopaminergic activity in the anterior hypothalamus of incubating hens may stimulate the release of unidentified prolactin-releasing factors and/or inhibit the release of LH by exerting an inhibitory influence in the area of the hypothalamus containing LHRH cell bodies.

The functional activity of hypothalamic 5-hydroxytryptamine neurones in broody bantam hens.

An assessment was made of the possible role of hypothalamic 5-hydroxytryptamine (5-HT) in the regulation of prolactin secretion in broody bantam hens. Prolactin secretion was stimulated less in incubating hens deprived of their nests for 24 h (nest-deprived) than in laying hens after administration of the 5-HT receptor agonist quipazine, or precursor 5-hydroxytryptophan. One type of 5-HT-binding site was found in the anterior and posterior hypothalami of out-of-lay, incubating and laying hens. Differences in prolactin secretion in these birds could not be accounted for by changes in the abundance of this type of 5-HT-binding site. Another type of 5-HT-binding site, with a higher density but lower affinity, was found in the anterior hypothalami of laying hens. No specific 5-HT-binding sites were found in the anterior pituitary gland. The turnover rates of 5-HT were compared in the anterior and posterior hypothalami of laying, incubating and nest-deprived hens. The turnover rates were estimated from the rate of accumulation of 5-HT after inhibiting its catabolism using the monoamine oxidase inhibitor, pargyline, or by measuring the ratio of the concentrations of 5-HT and its major metabolite, 5-hydroxyindole acetic acid. Both methods of measurement gave the same results. The turnover of 5-HT was increased in the anterior but not posterior hypothalami of incubating hens when compared with laying or nest-deprived hens. There was also a significant increase in turnover of 5-HT in the posterior hypothalami in nest-deprived hens when compared with laying or incubating birds.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of stimulation regimes and luteal phase support on the outcome of IVF.

Successful in-vitro fertilization (IVF) requires the generation of a number of healthy embryos and adequate priming and maintenance of a receptive endometrium. Both of these factors are influenced by ovarian stimulation regimes and are responsive to endocrine manipulation. Detailed analysis of follicular phase patterns of hormone secretion have established an inverse relationship between luteinizing hormone (LH) and egg/embryo quality which is not discernible on microscopic examination. The advent and extensive use of LHRH agonists in ovarian stimulation has gone some way towards optimizing embryo fitness by suppressing LH secretion and this has exposed the endometrial contribution to a failure of implantation to closer examination. The supraphysiological production of oestradiol and progesterone from the large numbers of follicles developed during ovarian stimulation cannot be without effect on the endometrium. Data presented in this brief review show how our understanding of ovarian stimulation and its influence on the outcomes of IVF has advanced and highlights the opportunities for manipulation of the endometrium to encourage implantation.

Relationships between prolactin, LH and broody behaviour in bantam hens.

The interactions between broody behaviour and changes in concentrations of plasma prolactin and LH were investigated in bantam hens. Adoption of newly hatched chicks caused incubating hens to leave their nests and prevented plasma prolactin decreasing as rapidly as in hens deprived of their nests and not given chicks. Further, the hens allowed to rear chicks came back into lay later (P less than 0.001) than the hens not allowed chicks. Plasma prolactin decreased and plasma LH increased in hens deprived of their nests: these changes were reversed when the hens re-nested. The changes in plasma LH and prolactin in nest-deprived and re-nesting birds were not always synchronous; this was particularly clear immediately after nest deprivation when the increase in plasma LH preceded the decrease in the plasma prolactin. Readiness to incubate disappeared between 48 and 72 h after nest deprivation and corresponded with the time when plasma prolactin decreased to baseline values. Administration of ovine prolactin depressed (P less than 0.01) the initial increase in plasma LH after nest deprivation, but repeated administration of prolactin for up to 72 h failed to suppress plasma LH to the values found in incubating hens. Repeated administration of ovine prolactin at 5- to 8-h intervals for 72 h maintained readiness to incubate in nest-deprived hens. It is concluded that the secretion of prolactin in broody hens is facilitated by the presence of chicks and that increased concentrations of plasma prolactin maintain incubation behaviour. In incubating hens the secretion of LH and prolactin may be partly regulated independently. In addition, LH secretion may also be inhibited by increased plasma prolactin.

Progesterone supplementation in the late follicular phase of an in-vitro fertilization cycle: a 'natural' way to time oocyte recovery?

Twenty-eight patients superovulated with clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) were given a single injection of 25 mg progesterone (P group) 4 h prior to the ovulation-inducing injection of human chorionic gonadotrophin (HCG). Plasma and urinary LH levels were significantly higher (P less than 0.05) in the P group immediately prior to HCG compared to controls. Plasma progesterone concentrations were also elevated (P less than 0.01) in the P group from the time of injection to oocyte recovery. The number of mature oocytes recovered was also higher (P less than 0.001; 59% versus 40% in controls) and the time interval between oocyte recovery and insemination was also shorter (P less than 0.01) in the P group. The pregnancy rate/replacement 15 days after oocyte recovery was 39% versus 23% in the P and control groups respectively. It was concluded that as more mature oocytes were recovered in the P group, progesterone supplementation in the late follicular phase may be beneficial for patients undergoing GIFT. This was borne out when the first two GIFT patients pretreated in this way became pregnant.

Short term use of an LHRH agonist to treat poor responders entering an in-vitro fertilization programme.

Seven patients who had previously responded poorly to stimulation with clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) and also exhibited high tonic urinary LH output (greater than 0.25 IU/h) were given an LHRH agonist (500 micrograms/daily) on days 1 to 3 of the menstrual cycle followed by exogenous gonadotrophin stimulation. During the latter stages of follicular development plasma and urinary LH output were significantly lower (P less than 0.01) than in the previous CC/HMG stimulated cycle. All seven patients had oocytes recovered, and embryos replaced. Three out of these seven became pregnant. To conclude, the efficacy of short term LHRH agonist treatment is equivalent to present longer term modes of administration in reducing gonadotrophin secretion and inhibiting the LH surge. The more widespread adoption of this abbreviated protocol could improve the prognosis for patients undergoing IVF in centres where facilities for intensive endocrine monitoring are not available.

Pregnancies after IVF when high tonic LH is reduced by long-term treatment with GnRH agonists.

Some patients show high output of urinary LH when superovulated with clomiphene citrate and HMG. Recent evidence has shown that this is detrimental to successful IVF. By the use of an GnRH analogue we have managed to ameliorate this condition and successfully establish pregnancy in these women. Further, the association between failure of IVF-ER and elevated levels of LH may explain the aetiology of some 'idiopathically' infertile couples.

The effect of progesterone supplementation prior to the induction of ovulation in women treated for in-vitro fertilization.

Thirty-one patients superovulated with clomiphene citrate (CC) and human menopausal gonadotrophin (HMG) were given a single injection of 25 mg progesterone (P group) 6 h prior to injection of human chorionic gonadotrophin (HCG). Levels of urinary and plasma luteinizing hormone (LH) were significantly higher (P less than 0.001) immediately prior to HCG in the P group compared with thirty-one control patients who had HCG on the same night. Plasma levels of progesterone remained significantly elevated (P less than 0.02) for 80 h after injection in the P group, thereafter the level was similar to controls. The number of oocytes recovered, fertilized and replaced per patient was identical in both groups. However, four control patients had no embryos replaced due to failed fertilization. It is concluded that in the majority of P patients the timing of ovulation induction by HCG injection was appropriate as an LH surge was elicited thus reflecting a physiological stage of readiness, and elevated plasma progesterone levels around the time of oocyte recovery and in the early luteal phase do not increase the likelihood of the establishment of pregnancy in patients stimulated for in-vitro fertilization and embryo replacement (IVF/ER) with CC and HMG.

Follicular development and early luteal function of conception and non-conceptional cycles after human in-vitro fertilization: endocrine correlates.

Two-hundred patients, half of whom had on-going pregnancies, were examined in terms of follicular growth, urinary oestrogen and LH output, oocytes recovered and embryos replaced. The two groups were identical in all parameters measured except that urinary LH output was significantly higher (P less than 0.01) in non-pregnant patients on the two days prior to HCG administration. During the early to mid-luteal phase, plasma progesterone concentrations were related to the number of follicles aspirated at oocyte recovery, but the overall pattern of secretion was similar in both groups. It is concluded that monitoring urinary LH output, a non-invasive technique, may be of great value for assessing oocyte quality and predicting the outcome of in-vitro fertilization and embryo replacement.