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Massive ascites associated with endometriosis is uncommon. Recurrent episodes of bloody ascites as a result of endometriosis occurred in a woman with familial Mediterranean fever, who underwent therapy for induction of ovulation. Ovulatory agents may provoke accumulation of ascites in patients with endometriosis.
Two experiments were conducted on White Leghorn hens to investigate the effect of different concentrations of LH on the frequency of induction of ovulation in vitro of ovarian follicles collected 18-20 h before the expected time of ovulation from birds of three different ages (7, 18 and 30 months) or of the same age but laying short (three to four) or long (more than seven) sequences of eggs. The ability of LH to induce ovulation was directly related to the age of the donors of the follicles. Follicles derived from hens laying short sequences of eggs were less responsive to the ovulation-inducing effects of LH than were follicles from birds laying long sequences. These observations suggest that the sensitivity of ovarian follicles to the ovulation-inducing effects of LH declines with age and is greater in hens laying long sequences of eggs than those laying short sequences.
Four women with unexplained infertility and two anovulatory oligomenorrheic women who experienced repeated premature luteinization when treated with human menopausal gonadotropin (hMG) or gonadotropin-releasing hormone (GnRH) were given the gonadotropin-releasing hormone agonist (GnRHa), luprolide acetate, in order to effect medical hypophysectomy. This was followed by hMG for induction of ovulation. Four of the six patients had hMG-only cycles, which were compared with the luprolide acetate/hMG cycles. The luprolide acetate/hMG cycles resulted in normal folliculogenesis with presumptive ovulation. In luprolide/hMG cycles, significantly more hMG was needed for induction of ovulation than in hMG-only cycles. Premature luteinization was abolished with luprolide acetate treatment.
Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to-estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome.
OBJECTIVE: To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility. DESIGN: Prospective. SETTING: Outpatient Infertility Clinic. PATIENTS: Ninety-five anovulatory women who conceived after gonadotropin therapy. INTERVENTION: Induction of ovulation by hMG and hCG monitored by plasma E2 measurements and ovarian ultrasonography. MAIN OUTCOME MEASURES: All follicles visualized on the day of hCG administration were recorded and divided into the following four groups: group I, 10 to 12 mm; group II, 13 to 15 mm; group III, 16 to 18 mm; and group IV, 19 mm and larger. The sonographic findings were statistically evaluated to 80 singletons and 45 multiple pregnancies. RESULTS: No statistical correlation was found to exist between the number of follicles from the different groups and the number of fetuses. CONCLUSIONS: The number and sizes of follicles visualized on the day of hCG administration have no predictive value regarding the occurrence of a multiple pregnancy.
The efficacy, safety, and patient's acceptance of intravenous and subcutaneous therapy with gonadotropin releasing hormone (GnRH) with the use of either an autoinfusion pump or a smaller manual pen pump delivery system have been evaluated during the induction of ovulation in outpatients with hypothalamic hypogonadotropic amenorrhea. An ovulatory response to intravenous GnRH was highly reproducible, even at low doses, and complications associated with the intravenous route of delivery were infrequent and readily treated. Although no complications were observed during subcutaneous GnRH therapy, the response to the subcutaneous route of delivery was unpredictable over a wide range of dosages and delivery schedules. The pen pump was rated more highly by subjects than the autoinfusion pump, because the pen pump was both light and inconspicuous.
Over the past 15 years, there has been a marked increase in the use of ovulation induction and intrauterine insemination (IUI) for the treatment of unexplained infertility. However, although ovulation induction and IUI have rapidly gained popularity, clinical use is based largely on practical experience rather than on well-designed scientific studies. This article summarizes the evidence in this area. Despite clinical heterogeneity and different methodological qualities of the trials, it can be concluded that ovulation induction significantly improves the probability of conception in couples with unexplained infertility, particularly when associated with IUI. It is remarkable, though, that there has been only one large-scale, randomized trial of ovulation induction plus IUI in the treatment of unexplained infertility in which one of the study arms is an untreated control group. For couples requiring treatment, the complication rate must be minimized, particularly the occurrence of high-order multiple pregnancy. Evaluation of the effectiveness and safety of low-dose gonadotrophin administration in patients with unexplained infertility is limited and further studies are warranted.
The objective of this study was to explore the effect of cotreatment with recombinant human growth hormone (GH), gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) for induction of ovulation in women with clomiphene resistant polycystic ovary syndrome (PCOS). It was designed as a randomized, double-blind, placebo controlled trial in which 30 women with anovulation associated with PCOS who were resistant to clomiphene all received DTRP6-LHRH (Decapeptyl microcapsules, 3.75 mg, i.m.) and, 2 weeks later, HMG in a standard, conventional, individually adjusted dose regimen until human chorionic gonadotrophin (HCG) and then luteal phase support could be given. From day 1 of HMG therapy, patients were randomized to receive either human GH (Norditropin, 12 IU/day, i.m., for 7 days) or placebo. The number of ampoules, duration of treatment and daily effective dose of HMG required to achieve ovulation, serum oestradiol concentrations and number of follicles induced, ovulation and pregnancy rates, serum insulin and insulin-like growth factor-I (IGF-I) concentrations were measured. There were no significant differences between growth hormone and placebo groups in any of the outcomes measured, other than a growth hormone induced increase in serum insulin and IGF-I levels. We conclude that although GH kinetics are abnormal and GH pituitary reserves generally low in women with PCOS, adjuvant GH treatment to GnRHa/HMG does not influence follicular development or sensitivity in response to gonadotrophins and that it does not seem likely to be of any potential clinical benefit for the treatment of PCOS.
Female mice from lines which had undergone long-term single trait and antagonistic index selection for litter size and body weight were analysed for ovulation rate and LH receptor induction. Compared to randomly selected controls, selection for large litter size increased ovulation rate (60%; P less than 0.001) and decreased LH receptor induction per microgram ovarian DNA (87%; P less than 0.01). Selection for large body weight increased ovulation rate (18%; P less than 0.001), but did not lead to a significant correlated response in LH receptor induction. Index selection for large litter size and small body weight increased ovulation rate (14%; P less than 0.01) and decreased LH receptor induction (72%; P less than 0.01), while index selection for small litter size and large body weight did not significantly alter either ovulation rate or LH receptor induction. LH receptor quantities in testes of males from the 5 lines did not exhibit the among-line profile which was observed in ovaries of females. These results confirm the role of ovulation rate in mediation of the positive genetic correlation between litter size and body weight in mice. Increased ovulation rate in mice selected for large litter size may be due to mechanisms associated with LH receptors as well as factors related to growth. In contrast, increased ovulation rate in mice selected for large body weight may be due exclusively to factors related to growth.
Prolonged postpartum acyclicity in suckled beef cows reduces the calf crop, and causes economic loss to beef cattle producers. Once anterior pituitary LH stores have been replenished between Days 15 and 30 post partum in suckled beef cows, methods to initiate cyclicity include non-hormonal methods such as weaning of calves (either complete, temporary or partial), or exposure to bulls, and hormonal methods such as administration of GnRH (either single injection, intermittent injections, or continuous infusion), gonadotropins (eCG, FSH, hCG), and steroids (estrogens, anti-estrogens, and progestogens). Weaning is costly, reduces growth rate of weaned calves, and short cycles are common after weaning-induced ovulation. Exposure of cows to bulls is not practical and its effect is not predictable. Repeated injections of GnRH, or a single injection of hCG are not always effective; ovulation is always followed by a short cycle, and usually a return to acyclicity. Estrogens and anti-estrogens do not consistently shorten postpartum anestrus. Exogenous progestogens include intravaginal devices, such as controlled-internal drug release (CIDR) or progesterone-releasing intravaginal device (PRID), norgestomet implants, and the feed-additive melengestrol acetate (MGA). Administration of exogenous progestogens is more practical than, and offers more advantages over, other treatments to shorten postpartum acyclicity in suckled beef cows. Mimicking the short cycle after Week 3 post partum, by maintaining circulating progesterone at subluteal concentrations or circulating progestin at intermediate concentrations, extends the life-span and allows terminal maturation of the postpartum dominant follicle as in cyclic cows, by initiating endogenous GnRH and LH pulses. This is followed by an LH surge, ovulation and normal cycles. The benefit from using exogenous progestogens after Week 3 post partum in suckled beef cows is that ovulation is induced, cyclicity is initiated, the resulting CL has a normal life-span and function, and there is no need to change management, such as weaning of calves. We present a model for the induction of ovulation and initiation of cyclicity using exogenous progestogens after Week 3 post partum in suckled beef cows.
OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.
The emphasis of this review is placed on the treatment of clomiphene-resistant women with polycystic ovary syndrome (PCOS) or with hypogonadotropic hypogonadism. There has been an increasing awareness of the need to avoid the consequences of multiple folliculogenesis, and this is reflected in the more widespread use of low-dose regimens for induction of ovulation, particularly in PCOS. The past 12 months have seen the first reports of the clinical applications of recombinant human follicle-stimulating hormone (FSH), and there is an intriguing suggestion that long-acting opiate agonists may have a part to play in the management of anovulation of hypothalamic origin.
In 25 women with disturbances of ovulation who were treated for sterility with D-Trp-6-LHRH, a potent analog of LHRH, ovulation was achieved in nine patients, but none of these became pregnant after therapy. After using the LHRH analog combined with clomiphene citrate in 14 of these 25 women, six ovulated and only one conceived. The overall rate of ovulation after the combined therapy was better than obtained when LHRH analog alone was administered. From this study we conclude that more investigations using different regimens have to be carried out in order to establish the clinical benefit of LHRH stimulatory analogs in induction of ovulation.
BACKGROUND: Subfertility in general practice is a common problem. However, most treatment is initiated in hospital. There may be a role for general practitioners in the treatment of some infertile patients. AIM: The aim of this study was to investigate the prevalence and management of infertility in women in general practice and to identify a specific cohort of patients potentially suitable for management in primary care. METHOD: The general practice notes of all women patients between the ages of 16 and 42 years who presented to their general practitioner with an infertility problem in the five years preceding July 1993 were analysed retrospectively. The patients were identified from the computer database of one Durham general practice. RESULTS: Fifty four cases were identified over the five year period, giving a prevalence of infertility in women in the practice of 15 per 1000 women. Of those who had a definite diagnosis made, 27% had an ovulatory disorder. Women with an ovulatory disorder tended to have a low serum day 21 progesterone level (90%); to present with primary infertility (80%); and to receive clomiphene as first line therapy (80%). The majority of ovulation induction therapy (95%) was initiated in secondary care. CONCLUSION: Ovulation induction therapy with clomiphene appears to be uncommon in general practice at present. Women requiring ovulation induction therapy may be a cohort of patients suitable for such management in general practice. These patients tend to present with primary infertility and to have a low mid-luteal progesterone level.
Data presented in this study indicate that ovulation can be induced in patients with PCOS using a GnRH analogue combined with hMG in a decreasing dose regimen. Based on the observed decline in functional, medium sized follicles in the late follicular phase, it may be speculated that the risk of ovarian hyperstimulation during gonadotropin induction of ovulation in patients with PCOS can be reduced.
We examined the relationships between the expression of the short and long forms of the prolactin (PRL) receptor (PRLR) mRNA in the ovary and changes in the levels of serum hormones such as sex steroid hormones and PRL during induction of ovulation in the rat. The expression of both forms of PRLR mRNA in the ovary was examined by Northern blot analysis in immature female rats treated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ovarian tissues and blood samples were obtained before treatment, 24 and 48 h after PMSG injection and 4, 6, 8, 12, 24 and 48 h after hCG treatment. Serum levels of 17beta-estradiol, progesterone and PRL were determined by radioimmunoassay. Serum levels of 17beta-estradiol rapidly increased to a maximal level 48 h after PMSG injection and then rapidly declined until 4 h after hCG injection. Serum levels of progesterone gradually increased after PMSG treatment, markedly increased to 114.2 nmol/l 8 h after hCG treatment and remained high until 48 h after hCG treatment. The serum level of PRL peaked at 66.2 microg/l (p < 0.01) 48 h after PMSG injection, and a temporary decrease after hCG treatment was followed by a continuously high level from 8 to 48 h. The expression of the long form of PRLR mRNA increased significantly (p < 0.01) to 688% of the control level after PMSG treatment, while that of the short form increased to only 184% of the control level. The expression of the long form of PRLR-mRNA rapidly declined until 6 h and then gradually increased until 48 h after hCG treatment. On the other hand, the expression of the short form of PRLR mRNA decreased to a nadir 12 h after hCG injection and then increased significantly (p < 0.01) to 142% of the control level. Our results showed that the changes in the short and long forms of PRLR mRNA differed in a time-specific manner and that these two forms are involved in different functions in the rat ovary during induction of ovulation. It is thought that the long form of PRLR mRNA is involved in folliculogenesis, while the short form of PRLR mRNA may play an important role in the formation and maintenance of the corpus luteum in the rat ovulatory cycle.
Twelve anovulatory women were examined by compound B-mode and real-time ultrasound scanning during incubation of follicular maturation and ovulation by human gonadotrophins. The treatment was monitored by daily serum oestrogen determinations. Ovarian follicles became visible on the ultrasound scans after 4 days of treatment, on average. The mean follicular diameter at that time was 8 mm. Multiple follicles developed in all but one of the 12 patients. At induction of ovulation the diameter of the dominant follicle varied between 15 and 22 mm. The serum oestrogen level was related to the number of follicles, the diameter of the greatest follicle and the ovarian size. There was a marked increase in the ovarian size during the treatment. The size of the uterus also increased. Ultrasound may be a valuable complement to daily oestrogen determinations for monitoring human gonadotrophin therapy.
Every effort should be made to find the cause of anovulation since specific therapy directed at correction of a specific hormonal deficiency or excess is, of course, much more effective than any empiric treatment. Moreover, some patients with disorders of ovulation may have serious, even fatal, underlying disorders. The use of thyroid or cortisone has been disappointing except in the treatment of an overt deficiency of thyroid or cortisone or an excess of adrenal androgens. Estrogens and progestational agents have not been consistently effective in the induction of ovulation. The use of clomiphene citrate, which apparently stimulates the release of gonadotropins, and the use of purified gonadotropins of human origin have been quite successful in the induction of ovulation in a variety of disorders of ovarian function. Because of real and potential hazards, the use of these new agents should be restricted to women for whom pregnancy is the primary goal or in whom standard methods of therapy have failed. Neither drug has been released by the Food and Drug Administration for routine clinical use.