Association between ectopic pregnancy and pelvic endometriosis.
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Adolescent↗
Biomedical subjects
J G Grudzinskas
Publications and source records attributed to J G Grudzinskas.
Hyperemesis gravidarum, a literature review.
Hyperemesis gravidarum (HG) is a condition causing severe nausea and vomiting in early pregnancy often resulting in hospital admission. The incidence of HG is approximately 0.5% of live births, said to be higher in multiple pregnancies, hydatidiform mole and other conditions associated with increased pregnancy hormone levels. Both the aetiology and pathogenesis of HG remain unknown. We conducted a literature review (1966-now) to summarize the current evidence on the aetiology and pathogenesis of HG. The potential role of pregnancy-related hormones such as progesterone, estrogen and HCG has been widely studied; however, various other hormones such as leptin, placental growth hormone, prolactin, thyroid and adrenal cortical hormones have been implicated in the aetiology of HG. In addition to endocrinological hypotheses, the rationale and evidence considering infectious, immunological, psychological, metabolic and anatomical causes for HG have been analysed here. Many studies suffer from the low number of patients included, the variable definition used for HG and varying assay methodology used in studies of hormone measurement. This review highlights the need for more extensive studies addressing the pathogenesis and aetiology of HG.
Adrenal Cortex↗
Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF.
BACKGROUND: The aim of this study was to evaluate the functional characteristics of granulosa cell populations of individual follicles of women undergoing controlled ovarian stimulation (COS) for IVF/ICSI in whom gonadotrophin had been withheld ('coasted') for the prevention of OHSS. METHODS: Follicular fluid and granulosa cells were isolated from 224 individual follicles in 41 women who had been coasted and from 257 individual follicles in 50 women who had a 'normal' response to COS. Cells were cultured at 10,000 cells per well, to evaluate progesterone secretion. Follicular fluid was assayed for progesterone and estradiol (E2). RESULTS: No significant differences were observed between the two groups with respect to granulosa cell number or follicular fluid progesterone and E2 and follicle size, the retrieval of an oocyte and the subsequent fertilization of the oocyte. However, the granulosa cells derived from the coasted group showed a higher rate of progesterone secretion per cell at 72 h which was sustained for longer. Differences were also seen at 72 and 120 h of culture with a loss of correlation between progesterone secretion and follicle diameter in the coasted group. CONCLUSIONS: Our findings suggest that coasting has an effect on the functional capacity of the granulosa cells and the duration of their function. It is likely that in women at risk of OHSS who are not coasted, the granulosa cells have the capacity to produce significantly more chemical mediators per cell and for a more prolonged period of time.
Adult↗
ART in recurrent miscarriage: preimplantation genetic diagnosis/screening or surrogacy?
Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. One approach uses either screening or diagnosis of embryonic chromosomes prior to embryo replacement [preimplantation genetic screening (PGS)/preimplantation genetic diagnosis (PGD)]. The second approach involves surrogacy. However, PGS/PGD assumes that the embryo is chromosomally abnormal, and that the mother should receive a chromosomally normal embryo. Surrogacy assumes that the embryo is normal and that the maternal environment needs to be substituted. This article examines the place of both techniques in different types of recurrent miscarriage, and tries to give guidelines as to which technique is preferable depending on the likelihood of an embryonic chromosome aberration. In repeated fetal aneuploidy or in the older patient, PGS or PGD are preferable. However, with high numbers of miscarriages, or in autoimmune pregnancy loss, surrogacy is preferable. In the light of recent work, it is uncertain which treatment mode is indicated in balanced parental chromosome aberrations. In conclusion, both techniques have a place, but probably only in those patients with a poor prognosis in whom assisted reproductive techniques will be shown to improve the subsequent live birth rate above the spontaneous rate.
Abortion, Habitual↗
The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome.
BACKGROUND: The aim of this study was to assess the effect of withholding gonadotrophins (coasting) during controlled ovarian stimulation (COS) on individual follicle concentrations of follicular fluid vascular endothelial growth factor (VEGF) in women at high risk of developing ovarian hyperstimulation syndrome (OHSS). METHODS: Twenty-two women who had been coasted and 26 optimally responding women (control group) undergoing COS for IVF were studied. At the time of oocyte retrieval, the follicular fluid from four to six individual follicles of different sizes was collected for VEGF analysis. RESULTS: A total of 118 follicles was analysed in the coasted group and 137 in the control group. A negative correlation was observed between the follicle size and VEGF concentration (r = -0.18, P = 0.03) in the control group, which was not seen in the coasted group. Similarly, the correlation between oestradiol (E(2)) and VEGF (r = 0.4, P < 0.0001) observed in the control group was not apparent in the coasted group. Significantly lower concentrations of VEGF were seen in the follicular fluid of the coasted patients. CONCLUSIONS: It is clear that there are differences in follicular fluid VEGF concentrations between the two groups. It is possible that coasting alters the capacity of the granulosa cells to produce VEGF and/or their response to hCG and in this way acts to reduce the severity and incidence of severe OHSS.
Adult↗
From basic research to clinical application of placental proteins--a workshop report.
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Adult↗
Excessive follicular response to controlled ovarian stimulation in a woman with menopausal FSH levels: case report.
A suspected poor responder to controlled ovarian stimulation (COS), with menopausal levels of follicular phase serum FSH, required coasting due to an excessive ovarian response. A 27 year old woman was referred to our Fertility Centre for ovum donation following repeated elevated, early follicular phase FSH levels (34.3, 27.1, 20.3 IU/l). Further investigations revealed the presence of antiovarian antibodies and a trial of COS, with the additional use of prednisolone, was proposed in view of her regular 28 day cycle. As 23 follicles were noted and an oestradiol level of 10,461 pmol/l following 7 days of stimulation with 450 IU of recombinant FSH per day, gonadotrophins were withheld for 9 days. Ten oocytes were retrieved and two grade I embryos were transferred. Pregnancy did not occur and she developed mild ovarian hyperstimulation syndrome. During a second cycle, multiple follicular development was again observed with an oestradiol level >13,200 pmol/l, despite a lower dose of gonadotrophin, and coasting was required for 4 days. Nineteen oocytes were collected, of which nine fertilized and cleaved. Two grade I embryos were replaced, leading to a singleton pregnancy. This patient subsequently had a vaginal delivery of a normal male baby at term. Young women with regular menstrual cycles and grossly elevated FSH levels may benefit from further investigation of autoantibodies and their ovarian response to exogenous gonadotrophins.
Adult↗
Prevention and treatment of ovarian hyperstimulation syndrome.
The ovarian hyperstimulation syndrome (OHSS) is a potentially fatal condition with a pathophysiology that is not clearly understood. A shift in fluid from the extravascular space occurs, thought to be induced by cytokines and/or vascular endothelial growth factor. Human chorionic gonadotrophin (hCG), exogenous or endogenous, seems to be the triggering mechanism, resulting in early and late development of the syndrome, respectively. The management of the syndrome is mainly symptomatic. Preventive strategies are being developed and constantly refined. Women at increased risk of OHSS need to be on the lowest possible dose of gonadotrophin with the aim of reducing the granulosa/luteal cell mass. Ultrasound and serum oestradiol (E2) measurements are, at present, the main methods used to identify and monitor those at risk during controlled ovarian hyperstimulation (COH). Withholding gonadotrophin stimulation (coasting), but continuing down-regulation, when a large number of follicles (greater than 20) and a rising serum oestradiol level are seen, is the most widely favoured and used preventive measure and the most cost effective. Management is symptomatic and aimed at achieving fluid balance, restoring plasma volume and improving renal function. This may be combined with an early resort to ascitic fluid aspiration, which will improve the feeling of wellbeing and may remove those agents responsible for the syndrome. Heparin, to prevent the risk of thromboembolism as a result of haemoconcentration, is important.
Chorionic Gonadotropin↗
Advances in the assessment of the uterus and fallopian tube function.
Hysterosalpingo-contrast-sonography (HyCoSy) using saline and Echovist is a well tolerated outpatient technique that provides a significant amount of information of relevance to the infertile woman that is not obtainable at hysterosalpingogram (HSG) whilst avoiding exposure to X-ray irradiation. When performed by experienced operators, it serves as a valuable, first-line screening test for the more invasive procedures of laparoscopy and dye chromopertubation and hysteroscopy. If detailed diagnostic information is required in women in whom there is no clinical or ultrasound evidence of pelvic pathology, the surgical technique of fertiloscopy can be considered to be appropriate. This technique permits confirmation that the ovum pick-up mechanism is normal, the tubes are patent and the uterine cavity is normal, while salpingoscopy and microsalpingoscopy permit the assessment of the tubal lumen.
Diagnostic Techniques, Obstetrical and Gynecologic↗
Male infertility.
Infertility affects 13-18% of couples and growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to pituitary disorders, testicular cancer, germ cell aplasia, varicocele and environmental factors or to defective sperm transport due to congenital abnormalities or immunological and neurogenic factors. Recent studies suggest an increased incidence of genetic disorders related to male infertility which may affect different levels, interfering with germ cell generation and maturation or leading to the production of non-functional spermatozoa. The identification of genetic causes of male infertility raises the issue of the transmission of defects to the offspring, a situation that is becoming more important given the increasing use of intracytoplasmic sperm injection (ICSI), a procedure in which the natural selection of the spermatozoa is by-passed. Fertilization can occur in vitro using ejaculated, epididymal or testicular spermatozoa, either fresh or frozen-thawed, providing opportunities hitherto not possible for men to be genetic fathers.
Chromosome Aberrations↗
Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study.
The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated to three groups to receive buserelin 150 microg nasal spray three times daily (Group B), nafarelin nasal spray 400 microg twice daily (Group N), or leuprorelin depot 3.75 mg once by intramuscular or subcutaneous injection (Group L) for pituitary desensitisation prior to commencing COH with human menopausal gonadotrophins (hMG) according to the Centre's protocol. The mean (+/-S.D.) age (years) (32.6+/-3.8: Group B, 32.1+/-3.3: Group N versus 32.1+/-3.3: Group L); mean (+/-S.D.) total dosage of hMG (ampoules) (37.5+/-16.1: Group B, 39.8+/-14.2: Group N versus 41.9+/-12.6: Group L) and mean daily dosage of hMG (ampoules) (3.1: Group B, 2.8: Group N versus 3.0: Group L) seen were not statistically significantly different. The duration between starting the different gonadotrophin-releasing hormone (GnRHa) and the beginning of the next menstrual period was also not seen to be statistically significantly different between the three groups (Group B: 10+/-5.5, Group N: 9.1+/-4.1 versus Group L: 8.2+/-3, days). The number of abandoned cycles was higher in Group L (17% versus 11.8%: Group B and 11.3%: Group N) but this difference did not reach statistical significance. The clinical pregnancy rates per oocyte retrieval and per embryo transfer procedure were respectively, 31.1, 35% in Group B, 12.8, 14% in Group N versus 20.5, 23.7 in Group L and were not seen to be statistically significantly different even when ongoing pregnancy rates were compared. Apart from a statistically significantly greater incidence of allergic nasal reactions in the nafarelin group (P=0.001), all other side-effects were not shown to be statistically significantly different between the three groups. We conclude that a single dose of leuprorelin depot can be considered to be as an equally effective alternative to multiple doses of buserelin or nafarelin for pituitary desensitisation in women undergoing COH for IVF.
Administration, Intranasal↗
'Early coasting' in patients with polycystic ovarian syndrome is consistent with good clinical outcome.
BACKGROUND: Coasting can be an effective strategy for the prevention of severe ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. However, OHSS may still occur in cases of excessive follicular response (i.e. >10 follicles/ovary and serum estradiol (E(2)) concentration >3000 pg/ml). Furthermore, prolonged coasting may result in a reduction of the oocyte retrieval rate and embryo quality. This pilot study investigates the potential of withholding gonadotrophins at an earlier stage, with the intention of minimizing these risks. METHODS: Gonadotrophin injections were withheld for a fixed period of 3 days once the leading follicle was 15 mm, whilst continuing pituitary down-regulation in 102 obese patients with polycystic ovarian syndrome (PCOS) in whom there was evidence of excessive ovarian follicular response (>10 follicles per ovary and serum E(2) >1500 but <3000 pg/ml). The events of ovarian stimulation, embryological and clinical outcomes were studied prospectively. RESULTS: The mean number of ampoules (75 IU per ampoule) of high purity (hp) FSH was 23.2. The mean serum E(2) level on coasting day 1 was 1943.7 and 2169.2 pg/ml on the day of HCG administration. Normal fertilization and cleavage rates were obtained despite early withdrawal of hpFSH in the obese PCOS patients, being 73.9 and 87.7% respectively. The clinical pregnancy rate was 45.1%. There were no cases of severe OHSS. Four patients suffered pregnancy-associated late-onset moderate OHSS. CONCLUSIONS: This pilot study suggests that withholding gonadotrophins at an earlier stage in patients with excessive ovarian follicular response at anticipated risk of developing severe OHSS in the course of ovarian stimulation is consistent with good embryological and clinical outcome in IVF and ICSI treatment cycles.
Adult↗
Value of measuring serum FSH in addition to serum estradiol in a coasting programme to prevent severe OHSS.
BACKGROUND: Withholding gonadotrophins (coasting) can reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) in patients having assisted reproduction therapy. This requires daily serum estradiol (E(2)) measurements, which occasionally have been seen to decline suddenly and sharply. METHODS: To increase the sensitivity of the coasting programme we measured serum FSH in parallel with E(2) in patients at risk of developing OHSS. RESULTS: Out of a total of 1240 cycles, 106 were coasted and in 89 both serum E(2) and FSH were measured at least twice during the coasting period. One case of late severe OHSS was encountered in the study group. The serum FSH declined by a rate of 24.3 +/- 4.5% per day. Serum E(2) level reached a 'safe level' of <10,000 pmol/l when the serum FSH declined to 5 IU/l or less. CONCLUSION: The results from this study show that measuring serum E(2) and FSH can assist in predicting the point at which serum E(2) has declined to a level safe enough to administer the trigger HCG.
Adult↗
Intrauterine insemination with frozen donor sperm. Pregnancy outcome in relation to age and ovarian stimulation regime.
BACKGROUND: The success of intrauterine insemination with donor semen (IUI-DI) is likely to be influenced by a number of variables, including age and ovarian stimulation (OS) regime. METHODS AND RESULTS: A retrospective analysis of 1056 treatment cycles in 261 women (212 single heterosexuals and 49 lesbians) was conducted to assess the influence of these two variables on pregnancy outcome during IUI-DI. The overall pregnancy rate was 10.6%, being 18.5% for women <35 years, 11.9% in women 35-40 years and 5.4% in women >40 years (P < 0.05). The cumulative pregnancy rate (CPR) after eight cycles was 0.86, 0.51 and 0.32 respectively (P < 0.05). A total of 445 inseminations were performed following spontaneous ovulation, 360 following OS with clomiphene citrate (CC) and 251 with hMG, the pregnancy rate per cycle being 13, 7.2 and 11.2% respectively. There was no statistically significant difference in the pregnancy rate per cycle, CPR or multiple pregnancy rate in the three treatment groups. CONCLUSIONS: These results indicate that the use of OS with either CC or hMG in women without ovulatory dysfunction does not improve the pregnancy rate during IUI-DI. The only factor associated with reduced effectiveness of fertility treatment was age, confirming that IUI is a poor treatment option for women >40 years of age.
Adult↗
High concentrations of CA 125 in uterine flushings: influence of cause of infertility and menstrual cycle day.
Uterine flushings were obtained under transvaginal ultrasonographic control from 132 women presenting for investigation and treatment of infertility. Levels of CA 125 were measured by radioimmunoassay and results expressed in relation to the total protein concentration of the same flushings. CA 125 was detected in uterine fluid at levels higher than those previously reported in peripheral blood. Uterine fluid CA 125 concentrations varied throughout the menstrual cycle, being highest in the mid-follicular phase (days 6 to 10). Uterine fluid CA 125 concentrations may reflect endometrial secretion of this protein more directly than serum levels. CA 125 concentrations did not vary according to the cause of infertility but further work in larger numbers of women is required.
Adult↗
Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study.
BACKGROUND: There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue. METHODS: We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children. FINDINGS: A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children. INTERPRETATION: This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.
Analysis of Variance↗
Prevention of severe ovarian hyperstimulation syndrome in IVF with or without ICSI and embryo transfer: a modified 'coasting' strategy based on ultrasound for identification of high-risk patients.
Ovarian hyperstimulation syndrome (OHSS) can be a severe and potentially life-threatening complication of ovarian stimulation for IVF. Coasting or withholding gonadotrophin stimulation relies on frequent estimation of serum oestradiol to identify patients at risk. A modified coasting protocol was developed in which identification of patients at risk of severe OHSS was based on ultrasound monitoring. Serum oestradiol concentrations were measured only in patients with >20 follicles on ultrasound (high risk). If serum oestradiol concentrations were <3000 pmol/l, the gonadotrophin dose was maintained; if concentrations were >/=3000 pmol/l but <13200 pmol/l and >/=25% of the follicles had a diameter of >/=13 mm, the gonadotrophin dose was halved; and if serum oestradiol concentrations were >/=13 200 pmol/l and >/=25% of the follicles had a diameter of >/=15 mm, patients were coasted. In the latter group, human chorionic gonadotrophin (HCG) 10000 IU was administered when at least three follicles had a diameter of >/=18 mm and serum oestradiol concentrations were <10000 pmol/l. Over a 10 month period, serum oestradiol concentrations were measured in 123 out of 580 cycles (24%) and in 50 cycles, gonadotrophins were withheld. Overall, moderate OHSS occurred in three patients (0.7%) and severe OHSS in one patient (0.2%). The pregnancy rates in the cycles where the gonadotrophin dose was reduced or withheld were 39.6 and 40% per cycle respectively; corresponding implantation rates were 30.7 and 25.6%. It is concluded that the modified coasting strategy is associated with a low risk of moderate and severe OHSS to a minimum without compromising pregnancy rates. Identification of patients at risk by ultrasound reduces the number of serum oestradiol measurements and thus inconvenience to patients as well as costs and workload.
Adult↗
Does laparoscopic ovarian diathermy affect the outcome of IVF-embryo transfer in women with polycystic ovarian syndrome? A retrospective comparative study.
Controlled ovarian stimulation for IVF and embryo transfer and outcome parameters were compared retrospectively in 31 women with clomiphene-resistant polycystic ovarian syndrome (PCOS). Of these women, 15 had previously undergone laparoscopic ovarian diathermy before IVF (group A, total 22 cycles) and 16 had not had surgical treatment (group B, total 24 cycles). No statistically significant differences were observed in the number of oocytes retrieved, although the number of embryos available for transfer was significantly higher in group B (7.1 +/- 3.8 versus 4.6 +/- 2.7, P < 0.01). The clinical pregnancy rate per embryo transfer appeared to be higher in group B (63.2 versus 41.2%), as did the miscarriage rate (66.7 versus 28.6%), giving an apparent improved ongoing pregnancy rate per embryo transfer in group A (29.4 versus 10.5%), but this was not statistically significantly different. The incidence of severe ovarian hyperstimulation syndrome (OHSS) was apparently higher in group B (4.2 versus 0%), but this difference was not statistically significant. No cases of severe OHSS were seen in group A. Ovarian diathermy does not appear to have a deleterious effect on controlled ovarian stimulation, and the outcome of IVF-embryo transfer may be beneficial in decreasing the risk of severe OHSS and improving the ongoing clinical pregnancy rate.
Adult↗