The efficacy of different hCG dose rates and the effect of hCG treatment on ovarian activity: ovulation, multiple ovulation, pregnancy, multiple pregnancy, synchrony of multiple ovulation; in the mare

Despite the widespread use of hCG to advance ovulation in the mare there is little information on efficacy of dose rates and any contraindications of its use. This study aims to investigate the effect of dose of hCG on ovulation within 48h and the effect of hCG on: ovulation, multiple ovulation (MO), pregnancy, multiple pregnancy (MP) rates and synchrony of MO; additionally whether any seasonal effect is evident. Sequential ultrasonic scanning was used to monitor the occurrence of ovulation, within 48h of treatment, in 1291 Thoroughbred mares treated with either 750iu hCG or 1500iu hCG s.c. Ovulation rate, type (single ovulations (SO), MO, synchronous, asynchronous) and subsequent pregnancy were then monitored in 1239 Thoroughbred mares on a commercial stud over 3 years, 536 of which were treated with 750iu hCG at mating, all mares were also allocated into groups according to month of mating. No significant difference existed between the two dose levels of hCG and no significant difference existed between treated and untreated mares in overall ovulations (1.32 and 1.28 respectively), MO (31.7% and 27.7%), pregnancy (65.1% and 65.6%) or MP rates (10.8% and 11.8%). There was no significant association between month of year and pregnancy or MP rates for either treated or control mares, nor for MO for untreated mares. A significant (p<0.05) association was evident between month and MO in treated mares, MO being lowest in April (22.3%). 95.9% of treated mares multiple ovulated within 48h compared with 90.7% controls, a near significant difference. In conclusion this study demonstrates that: (i) hCG dose of 750iu s.c. is just as effective in inducing ovulation within 48h as 1500iu, (ii) 750iu hCG has no significant effect on ovulation, MO, pregnancy or MP rates; (iii) a significant (p<0.05) association exists between season and MO in hCG treated mares; (iv) a tighter synchrony (ovulation within 48h) of MO is evident in hCG treated compared with control mares (p=0.052).     

Effect of GnRH treatment during the anovulatory season on multiple ovulation rate and on follicular development during the ensuing pregnancy in mares

Seasonally anovulatory mares were injected, i.m., twice daily with a GnRH analogue (GnRH-A), and hCG was given when the largest follicle reached 35 mm in diameter. In Exp. 1, treatment was initiated on 23 December when the largest follicle per mare was less than or equal to 17 mm. An ovulatory response (ovulation within 21 days) occurred in 17 of 30 (57%) GnRH-A-treated mares on a mean of 15.8 days. The shortest interval to ovulation in control mares (N = 10) was 57 days. The diameter of the largest follicle first increased significantly 6 days after start of treatment. In Exp. 2, treatment was begun on 15 January and mares were categorized according to the largest follicle at start of treatment. The proportion of mares ovulating within 21 days increased significantly according to initial diameter of largest follicle (less than or equal to 15 mm, 9/25 mares ovulated; 15-19 mm, 13/21; 20-24 mm, 20/24; greater than 25 mm, 3/3). The multiple ovulation rate was greater (P less than 0.01) for treated mares (27/86 mares had multiple ovulations) than for control mares (2/35). Treated mares in which the largest follicle at start of treatment was greater than or equal to 25 mm had a higher (P less than 0.01) multiple ovulation rate (9/14) than did mares in which the largest follicle was less than 25 mm (18/72). The pregnancy rate for single ovulators was not different between control mares (26/30 pregnant mares) and treated mares (43/54).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothalamic hypogonadism: induction of ovulation and pregnancy by subcutaneous pulsatile injections of gonadotrophin-releasing hormone

5 female patients with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone (GnRH), 2.5-15 micrograms every 90 min, for 2-6 months by means of an automated pump. This treatment produced an increase in serum LH, FSH, and estradiol levels in 4 patients, all of whom became pregnant. The estradiol levels failed to rise in 1 patient, in spite of an adequate LH and FSH response, and a subsequent biopsy showed evidence of primary ovarian failure in addition to the hypothalamic deficit. We conclude that subcutaneous pulsatile GnRH administration is a simple, safe, and relatively inexpensive way to induce ovulation in patients with hypothalamic hypogonadism.     

Conditional induction of ovulation in mice

Follicle-stimulating hormone controls the maturation of mammalian ovarian follicles. In excess, it can increase ovulation (egg production). Reported here is a transgenic doxycycline-activated switch, tested in mice, that produced more FSHB subunit (therefore more FSH) and increased ovulation by the simple feeding of doxycycline (Dox). The transgenic switch was expressed selectively in pituitary gonadotropes and was designed to enhance normal expression of FSH when exposed to Dox, but to be regulated by all the hormones that normally control FSH production in vivo. Feeding maximally effective levels of Dox increased overall mRNA for FSHB and serum FSH by over half in males, and Dox treatment more than doubled the normal ovulation rate of female mice for up to 10 reproductive cycles. Lower levels of Dox increased the number of developing embryos by 30%. Ovarian structure and function appeared normal. In summary, gene switch technology and normal FSH regulation were combined to effectively enhance ovulation in mice. Theoretically, the same strategy can be used with any genetic switch to increase ovulation (or any highly conserved physiology) in any mammal.     

Diagnosis of multiple pregnancy.

A study was made of 94 sets of twins born during 1975-8. Nine of these sets had not been diagnosed before labour started. Of the others, 75 were diagnosed as a result of clinical suspicion and 10 were diagnosed unexpectedly during the antenatal period, nine by ultrasonic examination. Thus, while ultrasonic examination has substantially reduced the incidence of undiagnosed twins, a fifth of all patients who had ultrasonography performed in the presence of a twin pregnancy were reported on at least one occasion to have a singleton pregnancy. Ultrasonography must be performed at least twice, therefore, before a multiple pregnancy can be confidently excluded.     

The effect of age on multiple ovulation rates, multiple pregnancy rates and embryonic vesicle diameter in the mare

Numerous and conflicting reports exist regarding factors that may effect mare reproductive performance, in particular multiple ovulation (MO) and its consequences. Sequential ultrasonic examination was used to monitor 3075 ovulations in 1581 mainly Thoroughbred mares to ascertain: whether increasing age is associated with an increase in MO; whether this is counteracted by an increase in embryo mortality (EM) prior to Day 13; and whether this embryonic loss may be associated with small-for-age embryonic vesicles (Days 13/14). Overall ovulation rate was 1.31, MO occurring in 29.3% of cycles. MO incidence significantly (p<0.05) increased with age (20.7% in 2-4-year olds compared to 35.6% in 17-19-year olds). 25.2% of MO were apparent as multiple pregnancies (MP) (40.0% of all pregnancies arising from MO) and 37.8% as single pregnancies (SP) at Days 13/14. Older mares demonstrated significantly (p<0.001) lower pregnancy rates and of those pregnant, significantly (p<0.01) fewer were MP than younger mares. Observation of 1442 embryonic vesicles failed to demonstrate any consistent significant association between age and vesicle size in single ovulating (SO) or MO mares on Days 13/14. We conclude that: (i) increasing age was significantly (p<0.05) associated with increasing incidence of MO; (ii) increasing age was significantly associated with a decreasing incidence of pregnancy/ovulation (p<0.001), and MP (p<0.01), at Days 13/14; (iii) there was no consistent significant association between mare age and vesicle size.     

Catabolite repression during single and multiple induction inEscherichia coli

Intracellular concentration of cAMP regulates the synthesis of enzymes sensitive to catabolite repression. The relationship between the single and multiple induction of beta-galactosidase (EC 3.2.1.23), L-tryptophanase (EC 4.1.99.1), D-serine deaminase (EC 4.2.1.14), L-asparaginase (EC 3.5.1.1) and L-malate dehydrogenase (EC 1.1.1.37) was studied and the effect of cAMP level on the induction in Escherichia coli Crookes (ATCC 8739) was investigated. A varying degree of catabolite repression was observed during induction of individual enzymes induced separately on different energy sources. The synthesis of l-tryptophanase was most sensitive, whereas l-asparaginase was not influenced at all. Exogenous cAMP was found to overcome partially the catabolite repression of beta-galactosidase and D-serine deaminase, both during single induction. The synthesis of l-malate dehydrogenase was negatively influenced by the multiple induction even in the presence of cAMP; on the other hand, the synthesis of l-tryptophanase was stimulated, independently of the level of the exogenous cAMP. Similarly, the activity of L-asparaginase slightly but significantly increased during the multiple induction of all five enzymes; here too the activity increase did not depend on exogenous cAMP.     

Birthweight discordance in multiple pregnancy.

This paper reviews several aspects of discordant growth in multiple pregnancies. Discordant growth is not a chance event and therefore several patterns can be discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15-25% (mildly) discordant, and about 5% are more than 25% (severely) discordant. Higher frequencies and increased severity are seen among triplets. Five observations regarding discordance became generally accepted: (a) not all discordant pairs are similar; (b) the larger the discordance level the greater is the risk for an adverse outcome; (c) discordant growth does not necessarily represent growth restriction; (d) a discordance level may have a different clinical implication in different gestational ages; and (e) the smaller fetuses in severely discordant pairs are at disproportionate risk for neonatal mortality. Mild discordance may represent a normal variation between sibs whereas severely discordant pairs often exhibit patterns of growth restriction. Not infrequently, discordance may represent an adaptation to the limited intrauterine space in order to increase gestational age.     

Loss in higher multiple pregnancy and multifetal pregnancy reduction.

From early pregnancy into childhood, higher multiples have much higher rates of mortality, whether from spontaneous abortion, the 'vanishing twin' syndrome, fetal or infant death. Many parents must cope with the death of one baby whilst the siblings remain critically ill or later become disabled and yet there grief is often underestimated. Little is known about the long term feelings of parents who choose to have a multifetal pregnancy reduction (MFPR). Most say they made the right decision but also that there was insufficient respect for their loss. They are often anxious about what, if anything, to tell the survivors and how they might react. Long term follow-up studies of the children as well as the parents are needed. Meanwhile parents who chose to have a MFPR must be given more information and ongoing support.