Imagine this clinical scenario: a commercial dairy cow farmer mentions they are identifying a high number of cows with ovarian follicular cysts during routine herd checks using ultrasound. The farmer asks you to recommend treatment that would return these cows to cyclicity as quickly as possible, given the negative economic impact of the condition.
You are aware exogenous hormones are the most commonly used and successful form of treatment. So, you decide to explore the literature to discover if there is evidence that gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG) results in a more rapid return to cyclicity.
Six studies were identified and appraised based on the predefined inclusion criteria. Five were randomised non-blinded comparative or controlled trials of level 3 (lower quality, controlled trials), per the levels of evidence described by Howick et al. (2011). One was a randomised controlled trial of level 2 (well-designed controlled trial) (Verma and Dabas, 1994).
The papers considered one or more of the following breeds: Holsteins, crossbred cattle, Friesians and Guernsey cattle.
GnRH and hCG therapy were used to treat cystic ovarian follicles in all the examined papers. All studies included the classification of ovarian follicular cyst size and observed cyst persistence of at least one week.
Three articles evaluated cattle for the presence of luteal tissue using ultrasound (Taktaz et al., 2015) or progesterone assays (Garverick et al., 1976; Nakao et al., 1992). Cystic ovarian follicles were identified using transrectal ultrasound or transrectal palpation.
Cystic ovarian follicles were identified using transrectal ultrasound or transrectal palpation
Sample size ranged from 20 to 150 cows, and the number of cows allocated for each treatment ranged from 3 to 70 animals. Three studies had groups of 30 to 70 animals per treatment (Mollo et al., 2012; Taktaz et al., 2015; Elmore et al., 1975), one study had treatment groups of 17 to 18 animals (Nakao et al., 1992) and two studies had treatment groups of 10 animals (Verma and Dabas, 1994; Garverick et al., 1976).
Clinical cure (defined as a return to oestrus or cyst luteinisation), first oestrus conception and interval to conception were consistently evaluated in most of the studies. Additionally, many studies evaluated parameters such as recovery time, overall conception rate, pregnancy rate, breedings per conception and interval to insemination.
Limitations included, but were not limited to, protocol drift, infrequent observations for oestrus detection, use of rectal palpation to classify cysts, lack of differentiation between follicular and luteal cysts, and retrospective exclusion of animals with luteal cysts.
Verma and Dabas (1994) used a negative control group with no treatment. They found no significant difference in clinical response or subsequent fertility between GnRH and hCG, though both therapies outperformed the control group. A higher percentage of animals treated with GnRH responded after one treatment than those treated with hCG. However, there were no significant differences in the number of animals that responded to either treatment or how quickly they responded to each treatment.
Recovery time as days to oestrus
Five out of six studies evaluated the recovery time as days to first oestrus. While no biological or statistically significant differences were found, the majority showed that hCG required fewer days to first oestrus than GnRH treatment (Mollo et al., 2012; Taktaz et al., 2015; Elmore et al., 1975).
Although Elmore et al. (1975) found that cattle treated with hCG required fewer days from treatment to first oestrus, the interval from treatment to conception was 10.4 days longer than in GnRH-treated animals. This may in part be because, on average, the hCG-treated cattle required more breedings per conception than the GnRH-treated group.
Although […] cattle treated with hCG required fewer days from treatment to first oestrus, the interval from treatment to conception was 10.4 days longer than in GnRH-treated animals
Garverick et al. (1976) reported conflicting results. Cattle treated with GnRH had a substantially shorter interval to conception (59.7 ± 9 versus 91 ± 23 days) compared to hCG treatment. They also required 2.7 fewer days from treatment to first oestrus or ovulation.
Verma and Dabas (1994), who reported findings as a range of days to first oestrus for each treatment, found significant overlap between the GnRH treatment (15 to 30 days) and hCG treatment (17 to 31 days).
Clinical cure as interval to conception
Findings were also divided when clinical cure was defined as the interval to conception.
Taktaz et al. (2015) and Nakao et al. (1992) found hCG treatment protocols required fewer days to conception, whereas Garverick et al. (1976) and Elmore et al. (1975) found that GnRH had a shorter interval to conception.
Nakao et al. (1992) evaluated clinical cure as luteinisation of the cystic ovarian follicle. The authors found that hCG luteinised 21.2 percent more cows than GnRH (14/17, 82.3 percent vs 11/18, 61.1 percent, respectively).
Additionally, Mollo et al. (2012) found that the hCG group outperformed alternative treatments in cure rate (the ratio between cows in oestrus within 30 days post-treatment and treated cows) and pregnancy rate (pregnant cows/treated cows). However, no statistical or biologically significant differences were detected.
In conclusion, there is currently insufficient evidence to suggest whether GnRH or hCG results in a more rapid return to cyclicity for cattle afflicted with cystic ovarian follicles. But given the weak evidence available, GnRH is currently a more appropriate first-line therapeutic for cystic ovarian disease due to the challenges surrounding the immunogenicity, availability and cost of hCG therapy.
GnRH is currently a more appropriate first-line therapeutic for cystic ovarian disease due to the challenges surrounding the immunogenicity, availability and cost of hCG therapy
It would be beneficial for further research to include:
- control groups
- spontaneous resolution of ovarian cysts
- route of hormone administration
- safest and most efficacious dose of hCG, given its capacity to cause the production of hCG antibodies and anaphylaxis in cattle
- network analysis comparing the efficacy of treatment methods once the literature can support the latter sufficiently
The application of evidence into practice should take into account multiple factors, not limited to individual clinical expertise, patient’s circumstance, owner’s values, the country, location and/or clinic where you work, the individual case in front of you and the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.